AU2006247027A1 - Leukemia disease genes and uses thereof - Google Patents

Description

WO 2006/125195 PCT/US2006/019614 PCT International Application Express Mail Mailing Label No. EV832483451US Attorney Docket No. WYE-035PC LEUKEMIA DISEASE GENES AND USES THEREOF TECHNICAL FIELD [0001] This invention relates to leukemia disease genes and methods of using the same for diagnosis and treatment of leukemia. BACKGROUND [00021 Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of bone marrow cell precursors characterized by variable clinical courses and outcomes. Approximately 30 percent of patients with MDS eventually progress to acute myelogenous leukemia (AML) and a clinical diagnostic assay especially suited to early identification of this subset of patients would help focus therapeutic options in these individuals. [0003] Recent expression profiling studies have revealed differences in AC 133 + hematopoeitic stem cell fractions from patients with MDS versus AML (Miyazato et al. (2001) Blood 98:422-427). Similar results have been observed in transcriptional profiles of CD34 cells purified from bone marrow of patients with MDS, which are radically altered from the transcriptional profiles of CD34 + cells from disease-free individuals (Hofmnann et al., (2002) Blood 100: 3553-3560). These studies, however, involved positive selection of specific cell subtypes, which is laborious and time-consuming. SUMMARY OF THE INVENTION [0004] The present invention features the use of peripheral blood samples containing peripheral blood mononuclear cells (PBMCs) for diagnosis or evaluation of the progression or treatment of AML and MDS. The present invention does not require positive selection of specific cell subtypes from the blood sample, thereby allowing rapid diagnosis and assessment of a leukemia. Accordingly, peripheral blood samples suitable for the present invention include, but are not limited to, WO 2006/125195 PCT/US2006/019614 whole blood samples or samples comprising un-fractionated PBMCs. In many cases, the peripheral blood samples employed comprise enriched un-fractionated PBMCs. By "enriched," it means that the percentage of PBMCs in a sample is higher than that in whole blood. In many cases, at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% of the cells in an enriched sample are PBMCs. Enriched un fractionated PBMCs can be prepared from whole blood by Ficoll gradients centrifugation or using cell purification tubes (CPTs). Other conventional methods can also be used to prepare enriched un-fractionated PBMCs. [0005] The invention provides genes whose expression profiles are indicative of the existence, status, progression or treatment of a leukemia. Leukemias that are amenable to the present invention include, but are not limited to, AML and MDS. For example, Table 4 recites genes differentially expressed in PBMCs from MDS patients versus PBMCs from disease-free subjects. Table 6 recites genes differentially expressed in PBMCs from AML patients versus PBMCs from MDS patients. Table 8 recites genes whose expression levels are useful for distinguishing humans with AML from humans with MDS, humans with AML from disease-free humans, and humans with MDS from disease free humans. Acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, or hairy cell leukemia may also be analyzed according to the present invention. [00061 Thus, in one aspect, the invention provides methods for diagnosis, or monitoring the occurrence, development, progression or treatment of leukemia (such as, for example, AML or MDS) in a subject using genes from Table 4 or Table 6. The methods include generating a gene expression profile from a peripheral blood sample from the subject and comparing the gene expression profile to one or more reference expression profiles (e.g. an expression profile representing a disease-free human, an expression profile representing a human with a leukemia, or an expression profile representing a human of borderline diagnosis). The gene expression profile and reference expression profiles include the expression patterns of one or more genes selected from Table 4 or 6 in PBMCs. In some embodiments, genes different from those recited in Table 2 are selected from Table 4 or 6, although genes recited in Table 2 can additionally be included. In some embodiments, the genes selected from Table 4 or 6 are those also recited in Table 8. 2 WO 2006/125195 PCT/US2006/019614 The difference or similarity between the gene expression profile and the one or more reference expression profiles is indicative of the presence, absence, occurrence, development, progression, or effectiveness of treatment of leukemia in the subject. The gene expression profile and the reference expression profiles can include the expression pattern of only one gene or of two or more (e.g. three or more, four or more, five or more, six or more, eight or more, ten or more, fifteen or more, twenty or more, forty or more, sixty or more, 100 or more, 200 or more, 300 or more, or 400 or more). In some embodiments, smaller numbers of genes (e.g. two, up to three, up to four, up to five, up to six, up to eight, up to ten, up to fifteen, up to twenty, up to forty, up to sixty, up to 100, or up to 200) are used. [00071 The expression profile of the leukemia disease gene(s) in a subject of interest can be determined by measuring the RNA transcript level of each of the gene(s) in a peripheral blood sample of the subject. Methods suitable for this purpose include, but are not limited to, quantitative RT-PCR, nucleic acid arrays, Northern blot, in situ hybridization, slot-blotting, and nuclease protection assay. The expression profile of the leukemia disease gene(s) can also be determined by measuring the protein product level of each of the gene(s) in the peripheral blood sample of the subject. Methods suitable for this propose include, but are not limited to, immunoassays (e.g., ELISA, RIA, FACS, or Western Blot), protein arrays, two dimensional gel electrophoresis, and mass spectroscopy. [00081 A typical reference expression profile employed in the present invention includes values or ranges that are suggestive of the expression pattern of the leukemia disease gene(s) in peripheral blood samples of disease-free humans or patients with known leukemias. In one example, a reference expression profile comprises the average expression levels of each of the leukemia disease gene(s) in peripheral blood samples of disease-free humans. In another example, a reference expression profile comprises the average expression levels of each of the leukemia disease gene(s) in peripheral blood samples of patients having a known leukemia. In still another embodiment, a reference expression profile comprises two or more individual expression profiles, each of which is the expression profile of the leukemia disease gene(s) in a peripheral blood sample of a different leukemia patient or disease-free human. In a further embodiment, a reference expression profile 3 WO 2006/125195 PCT/US2006/019614 comprises ranges that reflect variations in the expression levels of each of the leukemia disease gene(s) in peripheral blood samples of disease-free humans or patient with known leukemias. [0009] A reference expression profile employed in the present invention can be prepared using the same type of peripheral blood samples as the peripheral blood sample of the subject of interest and following the same preparation procedure and methodology. A reference expression profile can be predetermined or prerecorded. It can also be determined concurrently with or after the measurement of the expression profile of the subject of interest. [0010] The comparison of the expression profile of a subject of interest to a reference expression profile can be performed manually or electronically. The difference or similarity between the expression profile of the subject of interest and the reference expression profile is indicative of the presence or absence, or progression or non-progression, of leukemia in the subject. [0011] In some embodiments, the expression level of each of the leukemia disease genes employed in the comparison is correlated with a class distinction under a nearest-neighbor analysis or a significance analysis of microarrays. The class distinction represents an ideal expression pattern of the gene in un-fractionated PBMCs of disease-free humans and patients who have a specified leukemia (e.g., uniformly high in PBMCs of the disease-free humans and uniformly low in PBMCs of the leukemia patients, or vice versa). The disease status of a subject of interest (disease-free versus leukemia) can be predicted by comparing the expression profile of the leukemia disease genes in the subject of interest to a reference expression profile of the same genes using a k-nearest-neighbors or weighted voting algorithm. Based on the comparison, the subject from whom the sample was taken can be diagnosed with leukemia or diagnosed as disease-free; or an existing leukemia can be assessed for changes, such as those associated with progression or treatment. [0012] The invention also provides a general method for diagnosing or monitoring the occurrence, development, progression or treatment of MDS. The method includes generating a gene expression profile from a peripheral blood sample of a subject and comparing the gene expression profile to one or more reference expression profiles (e.g. an expression profile representing a disease-free 4 WO 2006/125195 PCT/US2006/019614 human, an expression profile representing a human with MDS, an expression profile representing a human with a non-MDS leukemia such as AML, or an expression profile representing a human of borderline diagnosis). The gene expression profile and the one or more reference expression profiles comprise the expression patterns of one or more MDS disease genes in PBMCs. The difference or similarity between the gene expression profile and the one or more reference expression profiles is indicative of the presence, absence, occurrence, development, progression, or effectiveness of treatment of MDS in the subject. The MDS disease genes can optionally include one or more genes selected from Tables 4, 6, or 8. The gene expression profile and the reference expression profiles can include the expression pattern of only one gene or of two or more (e.g. three or more, four or more, five or more, six or more, eight or more, ten or more, fifteen or more, twenty or more, forty or more, sixty or more, 100 or more, 200 or more, 300 or more, or 400 or more). In some embodiments, smaller numbers of genes (e.g. two, up to three, up to four, up to five, up to six, up to eight, up to ten, up to fifteen, up to twenty, up to forty, up to sixty, up to 100, or up to 200) are used. The comparison of the gene expression profile to the reference expression profiles can be done, for example, by a k-nearest neighbor analysis or a weighted voting algorithm. Based on the comparison, the subject from whom the sample was taken can be diagnosed with MDS or diagnosed as MDS-free or disease-free; or an existing MDS can be assessed for changes, such as those associated with progression or treatment. [0013] The invention also provides a method for identifying an MDS patient who is likely to progress to acute myelogenous leukemia (AML) using one or more genes from Table 6. The method includes generating a gene expression profile from a peripheral blood sample from an MDS patient and comparing the gene expression profile to one or more reference expression profiles (e.g. an expression profile representing a human with AML, an expression profile representing a human with MDS known to progress to AML, or an expression profile representing a human with MDS known not to progress to AML). The gene expression profile and the one or more reference expression profiles include the expression patterns in PBMCs of one or more leukemia disease genes selected from Table 6. The difference or similarity between the gene expression profile and the one or more reference 5 WO 2006/125195 PCT/US2006/019614 expression profiles is indicative that the MDS patient is likely to progress to AML. The leukemia disease genes selected from Table 6 are optionally different from those recited in Table 2, although genes from Table 2 could also be included. The leukemia disease genes selected from Table 6 are optionally among those also recited in Table 8. [00141 In another aspect, the present invention features methods for evaluating the effectiveness of a treatment of leukemia in a patient of interest. These methods comprise comparing an expression profile of at least one leukemia disease gene in a peripheral blood sample of the patient of interest to a reference expression profile of the same gene(s), where the peripheral blood sample is isolated from the patient after initiation of the treatment, and each of the leukemia disease gene(s) employed is differentially expressed in un-fractionated PBMCs of patients who have the leukemia being evaluated, as compared to in un-fractionated PBMCs of disease-free humans. In one example, the leukemia being assessed is MDS, and the leukemia disease gene(s) employed includes one or more genes selected from Table 4. An elimination or reduction in the difference between the expression profile of the leukemia disease gene(s) in the patient of interest and the corresponding expression profile in disease-free humans during the course of the treatment is indicative of the effectiveness of the treatment for the patient of interest. As compared to conventional methods, the gene expression profiling-based methods may have improved sensitivity for the detection of disease progression or remission. [0015] In still another aspect, the present invention features methods for evaluating the effectiveness of a treatment in preventing the progression of MDS to AML in a patient of interest. These methods comprise comparing an expression profile of at least one leukemia disease gene in a peripheral blood sample of the patient of interest to a reference expression profile of the same gene(s), where the peripheral blood sample is isolated from the patient after initiation of the treatment, and each of the leukemia disease gene(s) employed is differentially expressed in un fractionated PBMCs of MDS patients as compared to in AML patients. Examples of leukemia disease genes suitable for this purpose include, but are not limited to, those depicted in Table 6. The expression profile of the leukemia disease gene(s) in the 6 WO 2006/125195 PCT/US2006/019614 patient of interest during the course of the treatment is indicative of the effectiveness of the treatment in preventing the progression of MDS to AML in the patient. [0016] The invention also provides arrays useful, for example, for diagnosing MDS or other leukemias. The arrays include a substrate having several addresses; distinct probes, such as distinct nucleic acid sequences or distinct antibody variable regions, are disposed on each address. In some embodiments, at least 15% (or at least 30% or at least 50%) of the addresses have probes that can specifically detect MDS disease genes in PBMCs; the MDS disease genes are optionally selected from Table 4. In other embodiments, at least 15% (or at least 30% or at least 50%) of the addresses have probes that can specifically detect genes selected from Tables 4 or 6; the selected genes are different from those recited in Table 2, although genes from Table 2 could also be included. [00171 The invention also provides digitally-encoded expression profiles, as may be encoded in a computer-readable medium, useful, for example, as reference expression profiles to evaluate a gene expression profile from a peripheral blood sample. Each expression profile includes one or more digitally-encoded expression signals including a value representing the expression of a gene selected from Tables 4 or 6; the selected genes are different from those recited in Table 2, although digitally-encoded expression signals including values representing the expression of genes from Table 2 could additionally be included in the expression profile. The values in the digitally-encoded expression signals can represent, for example, the expression of the genes in a PBMC of a human with MDS or a human with AML. Each expression profile can include a single digitally-encoded expression signal or can include two, three, four, five, six, seven, eight, nine, or more digitally-encoded expression signals, such as at least ten, at least 20, at least 30, at least 40, at least 50, at least 100, or at least 200. [0018] In another aspect, the invention provides kits useful for diagnosis of a leukemia. In one embodiment, the kit includes one or more probes that can specifically detect MDS disease genes (optionally selected from Table 4) in PBMCs. The probes are optionally polynucleotides that hybridize under stringent or nucleic acid array hybridization conditions to the RNA transcripts, or the complements thereof, of the MDS disease genes, or, optionally, are antibody variable domains that 7 WO 2006/125195 PCT/US2006/019614 bind the products of the MDS disease genes. In another embodiment, the kit includes one or more probes that can specifically detect genes selected from Tables 4 and 6; the selected genes are different from those recited in Table 2, although probes for genes from Table 2 could additionally be included. Genes selected from Tables 4 and 6 can optionally be among those also recited in Table 8. The kits also include one or more controls, each representing a reference expression level of a gene detectable by the probes. 10019] In another aspect, the invention features a method of making a decision, e.g. selecting a payment class, for a course of treatment for a leukemia such as AML or MDS. The method includes assigning an individual to a class based on a value that is a function of the expression of one or more genes in a peripheral blood sample from the individual, thereby making a decision regarding the individual. The genes include one or more genes from among those recited in Tables 4 and 6 but not recited in Table 2, although the expression of genes recited in Table 2 could also be considered. In some embodiments, the one or more genes are selected from those also recited in Table 8. The decision can include, for example, selecting a treatment, such as an AML treatment, MDS treatment, other leukemia treatment, or an absence of treatment, based on the assignment of the individual to the class. The decision also can include administering or declining to administer a treatment based on the assignment; issuing, transmitting or receiving a prescription; or authorizing, paying for, or causing a transfer of funds to pay for a treatment. "Treatment" as used herein, refers to any action to deal with a disease or condition, regardless of whether the action is intended as preventative, curative, or palliative, for example; or to address a cause or symptom of the disease or condition; or to improve a second treatment by, for example, improving its efficacy or addressing a side effect. The decision may be recorded, such as in a computer-readable medium. [0020] The invention also features a method of providing information on which to make a decision about an individual. The method includes providing (e.g. by receiving) an evaluation of a subject, wherein the evaluation was made by a method described herein, such as by determining the level of expression of one or more genes in a peripheral blood sample of the subject, thereby providing a value. The genes include one or more genes from among those recited in Tables 4 and 6 but not 8 WO 2006/125195 PCT/US2006/019614 recited in Table 2, although the expression of genes recited in Table 2 could also be considered. The method also includes providing a comparison of the value with a reference value, thereby providing information on which to make a decision about the subject. The method can also include making the decision or communicating the information to another party, such as by computer, compact disc, telephone, facsimile, or letter. The decision can include selecting a subject for payment or making or authorizing payment for a first course of action if the subject demonstrates a gene expression level, pattern or profile observed in a leukemia (e.g AML or MDS) and a second course of action if the subject demonstrates a gene expression level, pattern or profile observed in a different leukemia (e.g. MDS or AML) or in leukemia-free humans. Payment can be from a first party to a second party. The first party can be a party other than the patient, such as a third party payor, an insurance company, employer, employer-sponsored health plan, HMO, or governmental entity. In some embodiments, the second party is selected from the subject, a healthcare provider, a treating physician, an HMO, a hospital, a governmental entity, or an entity that sells or supplies the drug. [0021] In one aspect, the invention features a method of making a data record. The method includes entering the result of a method described herein into a record, e.g. a computer readable record. In some embodiments, the record is evaluated and/or transmitted to a third party payor, an insurance company, employer, employer sponsored health plan, HMO, or governmental entity, or a healthcare provider, a treating physician, an HMO, a hospital, a governmental entity, or an entity which sells or supplies the drug. [0022] In one aspect, the disclosure features a method of providing data. The method includes providing data described herein, e.g., generated by a method described herein, to provide a record, e.g., a record described herein, for determining if a payment will be provided. In some embodiments, the data is provided by computer, compact disc, telephone, facsimile, email, or letter. In some embodiments, the data is provided by a first party to a second party. In some embodiments, the first party is selected from the subject, a healthcare provider, a treating physician, an HMO, a hospital, a governmental entity, or an entity which sells or supplies the drug. In some embodiments, the second party is a third party 9 WO 2006/125195 PCT/US2006/019614 payor, an insurance company, employer, employer sponsored health plan, HMO, or governmental entity. In some embodiments, the first party is selected from the subject, a healthcare provider, a treating physician, an HMO, a hospital, an insurance company, or an entity which sells or supplies the drug and the second party is a governmental entity. In some embodiments, the first party is selected from the subject, a healthcare provider, a treating physician, an HMO, a hospital, an insurance company, or an entity which sells or supplies the drug and the second party is an insurance company. [0023] In one aspect, the disclosure features a method of transmitting a record described herein. The method includes a first party transmitting the record to a second party, such as by computer, compact disc, telephone, facsimile, email, or letter. In some embodiments, the second party is selected from the subject, a healthcare provider, a treating physician, an HMO, a hospital, a governmental entity, or an entity which sells or supplies the drug. In some embodiments, the first party is an insurance company or government entity and the second party is selected from the subject, a healthcare provider, a treating physician, an HMO, a hospital, a governmental entity, or an entity which sells or supplies the drug. In some embodiments, the first party is a governmental entity or insurance company and the second party is selected from the subject, a healthcare provider, a treating physician, an HMO, a hospital, an insurance company, or an entity which sells or supplies the drug. [0024] Other features, objects, and advantages of the present invention are apparent in the detailed description that follows. It should be understood, however, that the detailed description, while indicating preferred embodiments of the invention, does so by way of illustration only, not limitation. Various changes and modifications within the scope of the invention will become apparent to those skilled in the art from the detailed description. DETAILED DESCRIPTION [00251 The present invention features the use of whole blood samples or samples comprising un-fractionated PBMCs for diagnosing or monitoring the progression or treatment of AML and MDS. Genes that are differentially expressed in un 10 WO 2006/125195 PCT/US2006/019614 fractionated PBMCs of AML (or MDS) patients as compared to in disease-free humans can be identified. These genes can be used as surrogate markers for diagnosing or evaluating the treatment of AML (or MDS) in a subject of interest. Genes that are differentially expressed in un-fractionated PBMCs of AML patients as compared to in MDS patients can also be identified. These genes can be used to monitor the progression of MDS in a patient of interest. The present invention does not require positive selection of specific cell subtypes (e.g., CD34 or AC 133), thereby allowing for rapid diagnosis and evaluation of AML and MDS. Other leukemias, such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, or hairy cell leukemia, can be similarly assessed according to the present invention. [00261 Various aspects of the invention are described in further detail in the following subsections. The use of subsections is not meant to limit the invention. Each subsection may apply to any aspect of the invention. In this application, the use of "or" means "and/or" unless otherwise stated. A. General Methods for Identifying Leukemia Disease Genes [00271 This invention features the use of nucleic acid arrays for the identification of genes that are differentially expressed in un-fractionated PBMCs of leukemia patients as compared to in disease-free humans or in patients who have a different type of leukemia. Nucleic acid arrays allow for quantitative detection of expression profiles of a large number of genes at one time. Non-limiting examples of nucleic acid arrays suitable for this purpose include Genechip ® microarrays (Affymetrix, Santa Clara, CA), cDNA microarrays (Agilent Technologies, Palo Alto, CA), and bead arrays (U.S. Patent Nos. 6,288,220 and 6,391,562). [0028] Polynucleotides to be hybridized to a nucleic acid array can be labeled with one or more labeling moieties to allow for detection of hybridized polynucleotide complexes. The labeling moieties can include compositions that are detectable by spectroscopic, photochemical, biochemical, bioelectronic, immunochemical, electrical, optical or chemical means. Exemplary labeling moieties include, but are not limited to, radioisotopes, chemiluminescent 11 WO 2006/125195 PCT/US2006/019614 compounds, labeled binding proteins, heavy metal atoms, spectroscopic markers (such as fluorescent markers or dyes), magnetic labels, linked enzymes, mass spectrometry tags, spin labels, electron transfer donors and acceptors, and the like. Polynucleotides to be hybridized to a nucleic acid array can be cDNA, cRNA, or other types of nucleic acid molecules. [0029] Hybridization reactions can be performed in absolute or differential hybridization formats. In the absolute hybridization format, polynucleotides derived from one sample, such as un-fractionated PBMCs from an AML or MDS patient or a disease-free human, are hybridized to the probes on a nucleic acid array. Signals detected after the formation of hybridization complexes correlate to the polynucleotide levels in the sample. In the differential hybridization format, polynucleotides derived from two biological samples, such as one from an AML or MDS patient and the other from a disease-free human, are labeled with different labeling moieties (e.g., Cy3 and Cy5, respectively). A mixture of these differently labeled polynucleotides is hybridized to a nucleic acid array. The nucleic acid array is then examined under conditions in which the emissions from the two different labels are individually detectable. [00301 Signals gathered from nucleic acid arrays can be analyzed using commercially available software, such as software provided by Affymetrix or Agilent Technologies. Controls, such as for scan sensitivity, probe labeling or cDNA quantitation, can be included in the hybridization experiments. In many embodiments, signals from nucleic acid arrays are scaled or normalized before being further analyzed. The expression signals of a gene can be normalized to take into account variations in hybridization intensities when more than one array is used under similar test conditions. Signals for individual polynucleotide complex hybridization can also be normalized using the intensities derived from internal normalization controls contained on each array. In addition, genes with relatively consistent expression levels across the samples can be used to normalize the expression levels of other genes. In one embodiment, the expression levels are normalized across the samples such that the mean is zero and the standard deviation is one. In another embodiment, the expression signals from a nucleic acid array are 12 WO 2006/125195 PCT/US2006/019614 subject to a variation filter which excludes genes showing minimal or insignificant variation across different classes of samples. [0031] Expression profiles in un-fractionated PBMCs of leukemia patients are compared to the corresponding expression profiles in disease-free humans. Genes that are differentially expressed in un-fractionated PBMCs of leukemia patients as compared to in un-fractionated PBMCs of disease-free humans can be identified. These genes are hereinafter referred to as leukemia disease genes. By "differentially expressed," it means that the average expression level of a leukemia disease gene in un-fractionated PBMCs of leukemia patients is statistically significantly different from that in un-fractionated PBMCs of disease-free humans. In many instances, the p-value of a Student's t-test (e.g., two-tailed distribution, two-sample unequal variance) for the observed difference is no more than 0.05, 0.01, 0.005, 0.001, 0.0005, 0.0001, or less. The average expression level of a leukemia disease gene in un-fractionated PBMCs of leukemia patients can be substantially higher or lower than that in disease-free PBMCs. For instance, the average expression level of a leukemia disease gene in PBMCs of leukemia patients can be at least 1, 2, 3, 4, 5, 10, 20, or more folds higher or lower than that in PBMCs of disease-free humans. Leukemia disease genes that are differentially expressed in patients who have different leukemias (e.g., AML versus MDS) can be similarly identified. [0032] Leukemia disease genes can also be identified using supervised or unsupervised clustering algorithms. Non-limiting examples of supervised clustering algorithms include the nearest-neighbor analysis, support vector machines, the SAM (Significance Analysis of Microarrays) method, artificial neural networks, and SPLASH. Non-limiting examples of unsupervised clustering algorithms include self-organized maps (SOMs), k-means, principal component analysis, and hierarchical clustering. [0033] The nearest-neighbor analysis, also known as the neighborhood analysis, is described in Golub et al., (1999) Science 286:531-537; Slonim et al., (2000) Procs. of the Fourth Annual International Conference on Computational Molecular Biology, Tokyo, Japan, April 8-11, pp. 263-272; and U.S. Patent No. 6,647,341, all of which are incorporated herein by reference. In the analysis, the expression profile of each gene is represented by an expression vector g = (el, e 2 , e 3 ,..., en), where ei 13 WO 2006/125195 PCT/US2006/019614 corresponds to the expression level of gene "g" in the ith sample. A class distinction can be represented by an idealized expression pattern c = (cl, c 2 , c 3 , . .. , cn), where ci = 1 or -1, depending on whether the ith sample is isolated from class 0 or class 1. Class 0 includes subjects having a first disease status (e.g., disease-free), and class 1 includes subjects having a second disease status (e.g. AML or MDS). Other forms of class distinction can also be employed. Typically, a class distinction represents an idealized expression pattern, where the expression level of a gene is uniformly high for samples in one class and uniformly low for samples in the other class. [0034] The correlation between gene "g" and the class distinction can be measured by a signal-to-noise score: P(g,c) = [pt(g) - ft2(g)]/[cI(g) + C2(g)] where tI(g) and j2(g) represent the means of the log-transformed expression levels of gene "g" in class 0 and class 1, respectively, and cai(g) and G2(g) represent the standard deviation of the log-transformed expression levels of gene "g" in class 0 and class 1, respectively. A higher absolute value of a signal-to-noise score indicates that the gene is more highly expressed in one class than in the other. In one example, the samples used to derive the signal-to-noise scores comprise enriched or purified un-fractionated PBMCs and, therefore, the signal-to-noise score P(g,c) represents a correlation between the class distinction and the expression level of gene "g" in un-fractionated PBMCs. The correlation between gene "g" and the class distinction can also be measured by other methods, such as the Pearson correlation coefficient or the Euclidean distance, as appreciated by those skilled in the art. [0035] The significance of the correlation between gene expression profiles in un-fractionated PBMCs and a class distinction can be evaluated using a random permutation test. An unusually high density of genes within the neighborhoods of the class distinction, as compared to random patterns, suggests that many of these genes have expression patterns that are significantly correlated with the class distinction. The correlation between genes and a class distinction can be diagrammatically viewed through a neighborhood analysis plot, in which the y-axis represents the number of genes within various neighborhoods around the class distinction and the x-axis indicates the size of the neighborhood (i.e., P(g,c)). 14 WO 2006/125195 PCT/US2006/019614 Curves showing different significance levels for the number of genes within corresponding neighborhoods of randomly permuted class distinctions can also be included in the plot. [0036] In many embodiments, the leukemia disease genes identified by the present invention are above the median significance level in the neighborhood analysis plot. This means that the correlation measure P(g,c) for each of these leukemia disease genes is such that the number of genes within the neighborhood of the class distinction having the size of P(g,c) is greater than the number of genes within the corresponding neighborhoods of randomly permuted class distinctions at the median significance level. The leukemia disease genes identified by the present invention can also be above the 40%, 30%, 20%, 10%, 5%, 2%, or 1% significance level. As used herein, x% significance level means that x% of random neighborhoods contain as many genes as the real neighborhood around the class distinction. [0037] The leukemia disease genes identified by the nearest-neighbor analysis can be used to construct class predictors. Each class predictor includes two or more leukemia disease genes, and can be used to assign a subject of interest to a disease status (e.g., AML, MDS, or disease-free). In one embodiment, a class predictor includes or consists of leukemia disease genes that are significantly correlated with a class distinction by the permutation test (e.g., genes above the 1%, 2%, 5%, 10%, 20%, 30%, 40%, or 50% significance level). In another embodiment, a class predictor includes or consists of leukemia disease genes that have top absolute values of P(g,c). [00381 The SAM method can also be used to correlate disease statuses with gene expression profiles in un-fractionated PBMCs. The prediction analysis of microarrays (PAM) method can be used to identify class predictors that can best characterize a predefined disease or disease-free class and predict the class membership of new samples. See, for example, Tibshirani et al., (2002) Proc. Natl. Acad. Sci. U.S.A. 99:6567-6572. [0039] The prediction accuracy of a class predictor of the present invention can be evaluated by k-fold cross validation, such as 10-fold cross validation, 4-fold cross validation, or leave-one-out cross validation. In a typical k-fold cross validation, the 15 WO 2006/125195 PCT/US2006/019614 data is divided into k subsets of approximately equal size. The model is trained k times, each time leaving out one of the subsets from training and using the omitted subset as the test samples to calculate the prediction error. Where k equals the sample size, it becomes the leave-one-out cross validation. [0040] Other methods can also be used to identify leukemia disease genes. These methods include, but are not limited to, quantitative RT-PCR, Northern Blot, in situ hybridization, protein arrays, immunoassays (e.g., ELISA, RIA or Western Blot), differential display, serial analysis of gene expression (SAGE), representation differential analysis (RDA), subtractive hybridization, GeneCalling@ (CuraGen, New Haven, CT), and total gene expression analysis (TOGA). Genes thus identified are differentially expressed in un-fractionated PBMCs of one class of subjects relative to another class of subjects, each class of subjects having a different disease status (e.g., AML, MDS, or disease-free). [0041] The above-described methods can also be used to identify genes whose expression profiles in un-fractionated PBMCs are predictive of different stages of leukemia progression, or different clinical responses of leukemia patients to a therapeutic treatment. For instance, gene expression profiles in PBMCs of MDS patients who eventually progress to AML can be compared to the corresponding gene expression profiles in MDS patients who do not progress to AML. Genes that are differentially expressed in these two classes of patients can be identified and used for the prediction of progression from MDS to AML. For another instance, leukemia patients can be grouped based on their responses to a therapeutic treatment. The global gene expression analysis is then used to identify genes that are differentially expressed in PBMCs of one group of patients versus another group. Genes thus identified are predictive of clinical outcome of a leukemia patient in response to the therapeutic treatment. B. Identification ofAML and MDS Disease Genes [0042] HG-U 133A Genechips@ (Affymetrix, Inc.) were used to identify AML or MDS disease genes. Genes that were differentially expressed in un-fractionated PBMCs of AML (or MDS) patients as compared to in disease-free humans were 16 WO 2006/125195 PCT/US2006/019614 identified. Genes that were differentially expressed in un-fractionated PBMCs of AML patients as compared to in MDS patients were also identified. [0043] Table 1 lists qualifiers on HG-U 133A Genechips® that showed elevated or decreased signals when hybridized to AML samples as compared to disease-free samples. Each qualifier in Table 1 corresponds to an AML disease gene which is differentially expressed in un-fractionated PBMCs of AML patients as compared to in disease-free humans. The hybridization signal at each qualifier represents the expression level of the corresponding gene in un-fractionated PBMCs. 100441 Table 1 also illustrates the average hybridization signals at each qualifier for AML ("AML Average") or disease-free samples ("Disease-Free Average"). The standard deviations of these signals ("AML StDev" and "Disease-Free StDev," respectively) are also provided. In addition, the ratios between AML and disease free hybridization signals ("AML/Disease-Free") and the p-values of Student's t test (two-tailed distribution, two-sample unequal variance) for the observed differences are provided. 17 WO 2006/125195 PCT/US2006/019614 Table 1. Genes Differentially Expressed in AML vs. Disease-Free PBMCs Qualifier AML AML Disease-Free Disease-Free AML/ P-value Average StDev Average StDev Disease-Free (unequal) 03948 s at 83 90.08 1.78 0.6 46.69 4.63E-06 203949 at 74.97 74.62 2.13 0.63 35.14 1.19E-06 206310 at 43.47 45.59 1.91 0.6 22.75 3.86E-06 209905 at 21.08 26.23 1 0 21.08 5.44E-05 14575 s at 36.92 53.62 1.84 0.52 20.02 3.88E-04 206871 at 35.58 46.76 1.93 0.94 18.41 1.23E-04 14651 s at 29.61 36.55 1.82 0.39 16.25 5.98E-05 10084_xat 14.5 18.69 1.02 0.15 14.18 1.20E-04 )5683 x at 20.42 29.24 1.47 0.5 13.92 4.32E-04 104798 at 35.69 23.65 2.76 0.68 12.95 7.41E-10 17023_x at 13.08 16.84 1.09 0.29 12.02 1.41E-04 [16474_x at 18.92 23.18 1.71 0.55 11.06 8.25E-05 102016 at 34.28 47.36 3.11 0.78 11.02 3.63E-04 )7134_x at 17.75 26.02 1.62 0.58 10.94 6.98E-04 15382_x at 15.19 17.97 1.4 0.5 10.85 5.25E-05 )5950 s at 101.03 143.73 9.31 13.71 10.85 5.23E-04 )5051 s at 16.39 18.21 1.6 0.5 10.24 2.37E-05 L 1709 _s at 32.19 29.76 3.2 0.79 10.06 1.23E-06 )513 _x at 12.31 15.08 1.29 0.46 9.55 1.02E-04 19054 at 14.61 13.58 1.76 0.43 8.32 2.05E-06 )4304 s at 12.47 10.57 1.62 0.49 7.69 4.74E-07 06674 at 15.97 13.11 2.16 0.64 7.41 2.90E-07 '7741 x at 14.33 16.08 1.96 0.3 7.33 5.05E-05 02589 at 32.89 33.91 4.64 2.3 7.08 1.63E-05 0783 x at 7.31 8.23 1.04 0.21 6.99 5.96E-05 1922 s at 38.47 29.59 5.73 1.84 6.71 1.13E-07 1427 s at 6.64 9.12 1 0 6.64 7.13E-04 06111 at 63.06 66.87 9.56 4 6.6 2.95E-05 2503 s at 25.86 23.52 4.04 1.94 6.39 2.92E-06 20377 at 6.28 7.57 1.02 0.15 6.14 1.93E-04 1310 s at 29.44 18.39 4.98 1.12 5.92 2.13E-09 19672_at 28.78 39.65 4.91 4.73 5.86 9.81E-04 05624_at 20.11 22.49 3.56 1.53 5.66 9.30E-05 05609._at 6.83 5.82 1.22 0.42 5.59 1.49E-06 06834_at 183.31 194.83 33.4 32.53 5.49 5.46E-05 01162 at 17.72 13.64 3.38 1.81 5.25 3.09E-07 01432_at 121.17 72.24 23.38 6.17 5.18 1.43E-09 4430 s at 5.86 7.6 1.13 0.34 5.17 6.73E-04 20416_at 9.64 7.98 1.87 0.34 5.16 1.24E-06 1743 s at 7.58 9.79 1.53 0.5 4.95 7.28E-04 31416_at 30.64 33.41 6.2 2.21 4.94 1.01E-04 18 WO 2006/125195 PCT/US2006/019614 Qualifier AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) 213150 at 8.39 10.1 1.71 0.46 4.9 3.44E-04 09543 s at 11.39 9 2.33 0.71 4.88 6.90E-07 213258_at 5.25 3.91 1.09 0.29 4.82 2.40E-07 10664 s at 5.89 5.35 1.24 0.43 4.73 8.77E-06 06067 s at 4.72 5.53 1 0 4.72 2.81E-04 09757 s at 4.69 4.26 1 0 4.69 8.72E-06 13515 x at 345.06 330.45 73.71 67.77 4.68 2.22E-05 19837 sat 5.72 6.62 1.24 0.43 4.6 2.68E-04 18899 s at 6.19 8.02 1.36 0.48 4.57 9.36E-04 210665 at 5.06 5.18 1.11 0.32 4.55 5.86E-05 206478 at 13.97 15.39 3.09 1.22 4.52 1.57E-04 01825 sat 11.22 8.13 2.49 0.66 4.51 2.04E-07 202441 at 20.61 12.29 4.62 1.51 4.46 3.52E-09 209160 at 9.64 11.28 2.2 0.76 4.38 3.56E-04 18788 s at 17.11 14.28 3.98 0.78 4.3 3.35E-06 219551 at 11.97 7.82 2.8 0.81 4.28 3.42E-08 01163 s at 19.17 12.42 4.49 2.06 4.27 2.92E-08 04419 x at 397.14 390.41 93.36 93.39 4.25 5.06E-05 209710 at 17.31 19.22 4.09 1.69 4.23 2.21E-04 201307 at 13.53 9.93 3.2 0.84 4.23 3.73E-07 213147 at 7.92 7.47 1.89 0.71 4.19 2.64E-05 203675 at 19.83 13.78 4.78 1.44 4.15 1.45E-07 21004 s at 14.44 12.46 3.51 1.27 4.11 7.39E-06 04848 x at 350.78 342.96 85.67 86.93 4.09 5.66E-05 05366 s at 4.39 4.7 1.13 0.34 3.87 2.03E-04 202252 at 14.53 9.36 3.76 1.23 3.87 5.11E-08 13110 s at 4.56 4.12 1.18 0.39 3.87 2.06E-05 219654 at 5.14 3.9 1.33 0.48 3.85 1.23E-06 18280 x at 75.11 62.63 19.58 4.15 3.84 6.14E-06 220232 at 8.14 5.68 2.13 0.66 3.82 2.74E-07 201324 at 8.75 9.34 2.36 0.93 3.71 2.34E-04 01892 s at 41.5 26.91 11.18 3.72 3.71 7.86E-08 218718 at 13.42 10.26 3.62 0.78 3.7 1.78E-06 209398_at 23.19 20.56 6.29 2.77 3.69 2.04E-05 201417 at 38.19 27.63 10.4 3.22 3.67 7.05E-07 201459_at 7.31 5.12 2.02 0.81 3.61 4.46E-07 18313 sat 7.83 5.61 2.18 0.49 3.6 6.70E-07 07459_x at 7.25 6.62 2.02 0.58 3.59 3.58E-05 14407 x at 7.72 8.29 2.16 0.47 3.58 2.91E-04 202502 at 6.92 4.56 1.93 0.39 3.58 1.42E-07 01418 s at 9.78 6.97 2.76 1.71 3.55 7.35E-07 14290 s at 168.36 110.3 48.13 13.86 3.5 1.53E-07 09790 s at 6.28 5.76 1.8 0.46 3.49 4.47E-05 19 WO 2006/125195 PCT/US2006/019614 S AML AML Disease-Free Disease-Free AML/ P-value )ualifier Average StDev Average StDev Disease-Free (unequal) 34069 at 8.19 8.72 2.36 0.61 3.48 3.01E-04 D3502 at 13.47 14.94 3.89 3.01 3.46 5.36E-04 9813 x at 30.97 36.16 9.04 4.22 3.42 9.06E-04 19218_at 4.86 4.24 1.44 0.5 3.37 2.70E-05 2444 s at 6.69 3.21 2.02 0.26 3.31 2.44E-10 01193_at 7.61 6.8 2.31 0.51 3.29 4.31E-05 2175 s at 12.56 7.35 3.82 0.98 3.28 2.59E-08 1013 s at 8.75 6.01 2.69 0.73 3.25 6.77E-07 05769 at 3.89 3.18 1.2 0.4 3.24 1.32E-05 08680 at 42.5 25.46 13.24 2.54 3.21 5.23E-08 12141 at 3.19 2.95 1 0 3.19 7.85E-05 3541 sat 4.86 2.52 1.53 0.5 3.17 2.40E-09 2036_sat 6.39 6.14 2.02 0.15 3.16 1.44E-04 ,0668 s at 6.08 3.9 1.93 0.39 3.15 2.45E-07 18847 at 8.67 3.51 2.76 1.38 3.15 2.96E-12 7294 s at 36.61 21.02 11.67 5.21 3.14 2.68E-08 5215 s_at 3.33 2.77 1.07 0.25 3.13 2.12E-05 13779 at 5.47 3.64 1.76 0.48 3.12 5.52E-07 18825 at 4.36 2.95 1.4 0.5 3.12 7.45E-07 2009 s at 3.81 2.69 1.22 0.42 3.11 1.68E-06 )5996 s _at 11.11 6.23 3.58 1.03 3.11 1.76E-08 .18729 at 4.89 4.04 1.58 0.5 3.1 2.14E-05 )9930 sat 11.42 6.97 3.69 1.35 3.09 1.09E-07 !18858 at 5.97 4.88 1.93 0.33 3.09 1.82E-05 L6153 xat 29.97 23.26 9.73 3.49 3.08 8.64E-06 )4409 s at 7.72 8.44 2.51 1.67 3.08 8.03E-04 105202 at 6.58 5.44 2.16 0.47 3.05 2.34E-05 35382 s at 46.89 39.19 15.36 5.37 3.05 2.83E-05 16920_sat 30.69 34.05 10.07 4.57 3.05 9.28E-04 109576_at 3.11 3.4 1.02 0.15 3.04 7.79E-04 32246 s at 11.17 5.49 3.69 0.9 3.03 1.18E-09 Z12115 at 3.69 3.83 1.22 0.56 3.02 4.78E-04 104168_at 9.67 5.87 3.2 0.97 3.02 1.25E-07 11820 x at 3.61 3.84 1.2 0.4 3.01 6.29E-04 15806 x at 31.5 33.49 10.53 5 2.99 6.66E-04 05768_s at 3.31 2.71 1.11 0.32 2.98 2.58E-05 10829 s at 6.28 5.19 2.11 0.44 2.97 2.80E-05 08107_sat 4.03 3.11 1.36 0.48 2.97 1.07E-05 200923_at 10.36 9.66 3.49 1.12 2.97 1.47E-04 03116 s at 21.44 21.93 7.22 5.62 2.97 5.10E-04 04900 x at 7.83 7.26 2.64 0.83 2.96 1.38E-04 02845 s at 10.08 6.03 3.42 2.08 2.95 1.36E-07 203787 at 6.92 5.81 2.36 0.48 2.94 3.89E-05 20 WO 2006/125195 PCT/US2006/019614 AML AML Disease-Free Disease-Free AML/ P-value ?ualifier Average StDev Average StDev Disease-Free (unequal) p4170_s at 6.92 3.81 2.36 0.53 2.94 2.14E-08 01413 at 10.03 5.78 3.42 0.92 2.93 5.86E-08 01054 at 11.72 7.27 4.02 1.2 2.91 2.70E-07 01952 at 12.81 10.38 4.42 1.48 2.9 2.70E-05 04647_at 8.94 8.61 3.09 0.9 2.9 2.54E-04 09892 at 27.53 24.22 9.51 3.7 2.89 8.53E-05 19789 at 4.94 3.59 1.71 0.46 2.89 4.95E-06 )2946 s at 5.89 5.45 2.04 0.21 2.88 1.59E-04 04011 at 5.5 5.81 1.91 0.42 2.88 7.38E-04 .4909 sat 11.25 6.93 3.91 1.29 2.88 2.71E-07 14391 x at 7.97 3.36 2.78 0.7 2.87 4.74E-11 13035 at 10.75 7.04 3.8 1.06 2.83 9.99E-07 .4657 s at 7.83 5.17 2.78 0.88 2.82 1.23E-06 [0613 s at 7.94 4.79 2.82 0.86 2.81 2.23E-07 )0615 s at 6.36 3.59 2.27 0.89 2.81 6.19E-08 5537_xat 12.36 8.06 4.42 1.83 2.8 1.10E-06 106480 at 2.92 2.41 1.04 0.21 2.79 4.45E-05 .2067 x at 13.25 9.5 4.78 1.52 2.77 5.86E-06 104173_at 6.33 2.39 2.29 0.55 2.77 4.04E-12 112268 at 43.75 24.26 15.89 3.52 2.75 5.30E-08 )1309 x at 5.5 3.18 2 0.43 2.75 1.23E-07 15182 x at 6.72 3.61 2,44 0.62 2.75 2.81E-08 101037 at 16.86 11.29 6.13 1.46 2.75 1.97E-06 114236 at 4.69 4.62 1.71 0.46 2.74 4.55E-04 10644 s at 20.72 11.39 7.56 2.2 2.74 4.64E-08 )6323_x at 68.94 44.22 25.16 7.82 2.74 9.69E-07 101563 at 6.67 4.33 2.44 0.55 2.73 1.24E-06 [3301 _xat 6.83 3.08 2.51 0.59 2.72 5.42E-10 118039 at 7.06 4.54 2.6 0.62 2.71 1.12E-06 112174 at 18.47 12.28 6.82 1.72 2.71 2.03E-06 118069 at 8.83 6.68 3.27 1.3 2.7 1.77E-05 16202_sat 11.42 9.55 4.22 1.52 2.7 7.19E-05 11014 s at 6.83 4.72 2.53 0.63 2.7 4.10E-06 )2564 x at 5.69 3.05 2.11 0.75 2.7 3.35E-08 03588 s at 10.83 7.22 4.02 1.18 2.69 2.26E-06 08864 s at 35.33 16.41 13.18 3.66 2.68 1.41E-09 18883 s at 10.42 7.78 3.89 0.86 2.68 1.49E-05 15489_x at 9.69 9.52 3.62 1.05 2.68 5.30E-04 09360 s_at 8.19 4.89 3.07 1.07 2.67 3.42E-07 201503 at 6.75 5.41 2.53 0.59 2.66 4.32E-05 203282 at 8.08 4.91 3.04 0.74 2.66 4.98E-07 00696 s_at 24 12.45 9.07 2.36 2.65 2.10E-08 217869_at 16.92 9.81 6.4 1.47 2.64 2.13E07 21 WO 2006/125195 PCT/US2006/019614 AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) )8579_xat 20.39 15.09 7.73 2.14 2.64 1.53E-05 13129 sat 5.14 3.39 1.96 0.21 2.63 2.36E-06 18342 s at 8.92 4.56 3.4 0.99 2.62 1.78E-08 34026 sat 6.69 5.11 2.56 0.62 2.62 2.53E-05 39825 s at 4.94 2.77 1.89 0.38 2.62 1.18E-07 39179 s at 14.14 7.86 5.42 1.6 2.61 1.09E-07 Z17975 at 4.22 3.3 1.62 0.49 2.6 3.93E-05 17791 s at 7.11 3.71 2.73 0.75 2.6 3.00E-08 08967 s at 11.47 5.19 4.42 0.87 2.59 1.23E-09 202371 at 8.64 5.83 3.33 0.8 2.59 4.15E-06 212055 at 9.67 6.17 3.73 1.32 2.59 1.69E-06 200703 at 16.92 13.59 6.56 2.25 2.58 6.22E-05 32262 x at 12.42 6.88 4.82 1.45 2.57 1.20E-07 209200 at 3.31 3.14 1.29 0.46 2.56 5.08E-04 13572 s at 41.53 24.93 16.2 4 2.56 6.00E-07 10762_s at 4.78 3.99 1.87 0.4 2.56 1.07E-04 00658 s at 9.78 6.12 3.82 1.28 2.56 1.37E-06 10999 s at 5.11 3.43 2 0.21 2.56 4.21E-06 05518 s at 7.94 3.85 3.11 0.68 2.55 7.90E-09 217809 at 26.75 12.88 10.49 2.16 2.55 6.77E-09 20725 x at 15.72 8.62 6.2 1.25 2.54 1.18E-07 08857 s at 6.03 4.17 2.38 0.58 2.54 7.84E-06 210401 at 16.5 7.44 6.51 2.37 2.53 1.55E-09 201555 at 11.86 8.32 4.69 1.08 2.53 9.94E-06 02708 s at 19.72 16.67 7.8 2.69 2.53 1.43E-04 01826_s at 5.06 2.66 2 0 2.53 5.32E-08 11684 s at 11.61 6.56 4.6 1.19 2.52 2.26E-07 201951 at 3.42 2.68 1.36 0.48 2.52 5.47E-05 01564 s at 3.47 2.83 1.38 0.49 2.52 9.43E-05 01897 s at 6.81 4.76 2.71 0.59 2.51 1.03E-05 213395 at 5.56 2.8 2.22 0.64 2.5 2.54E-08 08690 s at 30 17.54 12.02 3.06 2.5 5.11E-07 204565 at 5.03 2.32 2.02 0.26 2.49 4.01E-09 01015 sat 6.72 5.47 2.71 1.67 2.48 1.26E-04 209409 at 4.81 3.05 1.96 0.21 2.46 2.57E-06 08490 x at 9.44 7.09 3.84 1.26 2.46 3.84E-05 203560 at 4.64 3.86 1.89 0.32 2.46 1.44E-04 213170_at 7.03 2.97 2.87 0.63 2.45 5.82E-10 205227_at 3.81 2.96 1.56 0.5 2.45 6.61E-05 18927_s at 6.08 4.29 2.49 1.06 2.44 1.69E-05 09318 x at 5.92 3.99 2.42 0.5 2.44 7.63E-06 00783 sat 5.75 4.29 2.36 0.86 2.44 3.75E-05 213346_at 6.11 4.14 2.51 0.51 2.43 8.55E-06 22 WO 2006/125195 PCT/US2006/019614 Qualifier AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) 205418 at 4.97 4.29 2.04 0.77 2.43 2.60E-04 02107 s at 12.08 9.55 4.98 1.06 2.43 8.20E-05 204082 at 10.89 8.83 4.49 0.92 2.43 1.15E-04 202862 at 5.33 2.98 2.2 0.46 2.42 3.03E-07 212526 at 4.89 3.08 2.02 0.15 2.42 2.71E-06 10358 x at 7.31 4.48 3.02 0.99 2.42 1.91E-06 20615 sat 3.92 3.71 1.62 0.49 2.41 7.40E-04 201938 at 28.17 16.22 11.73 2.54 2.4 6.26E-07 201202 at 11.14 9.72 4.64 1.48 2.4 3.25E-04 00648 s at 27.33 24.54 11.42 5.94 2.39 5.01E-04 01277 sat 30.36 19.61 12.71 2.46 2.39 4.92E-06 10044 s at 11.19 4.9 4.69 2.14 2.39 2.22E-09 14501 s at 61.94 30.01 25.98 5.58 2.38 2.15E-08 206589 at 6.03 4.12 2.53 1.24 2.38 1.56E-05 01240 s at 19.72 11.22 8.33 3.05 2.37 6.69E-07 08626 s at 14.83 7.22 6.29 1.52 2.36 2.87E-08 205349 at 22.08 15.46 9.4 4.4 2.35 2.52E-05 16833 x at 4.75 4.18 2.02 0.26 2.35 4.00E-04 216609 at 9.69 4.7 4.13 1.84 2.35 3.31E-08 218026 at 9.22 5.9 3.93 0.86 2.34 5.33E-06 11464 x at 3.33 2.03 1.42 0.5 2.34 2.51E-06 08677 s at 10.56 4.99 4.51 1.41 2.34 1.72E-08 16981_x at 8.11 2.35 3.47 0.89 2.34 2.27E-14 203744 at 5.25 1.63 2.24 0.43 2.34 2.96E-13 218461 at 4.72 3.33 2.02 0.15 2.34 2.47E-05 01036 s at 5.22 3.55 2.24 0.43 2.33 1.53E-05 05600 x at 7.08 3.68 3.04 1 2.33 1.45E-07 07002 s at 5.11 3.09 2.2 0.55 2.32 2.31E-06 11713 x at 4.17 3.41 1.8 0.5 2.31 2.05E-04 08818 s at 21.83 11.69 9.44 2.24 2.31 2.69E-07 219007 at 5.33 3.59 2.31 0.7 2.31 1.48E-05 201619 at 13.22 8.5 5.73 1.98 2.31 7.59E-06 01231 s at 101.25 40.88 43.93 7.96 2.3 5.73E-10 221471 at 8.08 3.71 3.53 0.81 2.29 1.27E-08 16705 s at 10.56 5.94 4.62 1.34 2.28 8.43E-07 212415 at 14 8.68 6.13 1.56 2.28 4.60E-06 05601 s at 5.53 3.87 2.42 0.58 2.28 3.00E-05 209208 at 6.58 3.5 2.89 0.83 2.28 3.02E-07 202309 at 9.72 6.08 4.27 0.89 2.28 5.23E-06 201218 at 4.56 3.05 2 0.37 2.28 1.50E-05 18188 s at 7.83 3.71 3.44 0.72 2.27 2.80E-08 00983_x at 12.58 8.09 5.53 1.42 2.27 8.67E-06 08964 s_at 10.31 4.05 4.53 0.87 2.27 3.72E-10 23 WO 2006/125195 PCT/US2006/019614 Qualifier AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) 210365 at 8.78 5.84 3.87 1.62 2.27 1.71E-05 20741 sat 8.92 5.11 3.93 1.23 2.27 1.33E-06 03589 s at 5.53 3.04 2.44 0.59 2.26 6.20E-07 201664 at 16.97 10.4 7.51 1.55 2.26 4.16E-06 08527 xat 9.03 5.15 4 0.95 2.26 1.27E-06 201448 at 4.61 3.09 2.04 0.21 2.26 1.72E-05 05692 s at 6.11 3.85 2.71 1.08 2.25 7.70E-06 17727_xat 17.36 9.58 7.71 2.93 2.25 8.03E-07 217786_at 6.5 3.55 2.89 0.88 2.25 6.22E-07 18585 s at 3 2.65 1.33 0.48 2.25 6.54E-04 05608 s at 5.69 2.69 2.53 0.59 2.25 3.35E-08 205453 at 15.08 11.26 6.73 2.31 2.24 9.34E-05 04386 s at 25.72 13.32 11.51 2.57 2.23 2.36E-07 10052 s at 4.42 2.47 1.98 0.4 2.23 9.78E-07 209111 at 5.11 2.12 2.29 0.51 2.23 1.99E-09 208898 at 5.06 2.56 2.27 0.54 2.23 1.62E-07 200821 at 13.83 6.62 6.24 1.68 2.22 5.72E-08 07719 x at 9.06 2.68 4.09 0.9 2.21 2.09E-13 09199 s at 9.83 6.95 4.44 1.59 2.21 5.25E-05 214500 at 7.22 6.2 3.27 0.99 2.21 5.45E-04 209806 at 43.28 21.85 19.58 5.29 2.21 1.77E-07 01028 s at 55.5 32.88 25.16 5.38 2.21 3.32E-06 16554 s at 25.67 7.76 11.64 2.1 2.2 5.42E-13 218099 at 4.75 3.76 2.16 0.52 2.2 2.18E-04 21581 s at 24.86 12.8 11.29 2.6 2.2 2.72E-07 22294_s at 7.39 5.81 3.36 1.05 2.2 2.12E-04 203688 at 4.69 2.79 2.13 0.55 2.2 3.64E-06 200728 at 49.89 15.96 22.71 5.86 2.2 2.37E-12 01562 s at 5.42 1.5 2.47 0.73 2.2 1.75E-14 203608 at 3.75 2.14 1.71 0.73 2.19 2.43E-06 11714_xat 60.39 32.21 27.58 4.67 2.19 5.66E-07 06057_xat 8.36 2.77 3.82 0.96 2.19 7.42E-12 07761 s at 25.67 15.98 11.73 2.31 2.19 8.33E-06 12739 sat 8.17 3.5 3.73 1.12 2.19 6.36E-09 01060_x at 19.39 7.18 8.87 2.46 2.19 1.65E-10 00769 s at 5.78 2.82 2.64 0.71 2.18 1.09E-07 06445 s at 24 10.31 11 2.39 2.18 6.92E-09 08858 sat 11.89 5.96 5.47 2.03 2.17 2.26E-07 202546 at 49.39 24.62 22.71 6.17 2.17 1.82E-07 18279_s_at 4.44 3.33 2.04 0.3 2.17 1.25E-04 03253 s at 9.11 4.01 4.2 0.94 2.17 1.36E-08 209177 at 5.25 2.96 2.42 0.66 2.17 1.92E-06 10549_s at 2.17 1.92 1 0 2.17 8.57E-04 24 WO 2006/125195 PCT/US2006/019614 AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) 1329 sat 14.92 12.27 6.91 3.99 2.16 5.35E-04 '1301 s at 9.25 6.86 4.29 1.83 2.16 1.42E-04 01589_at 7.47 5.37 3.47 0.79 2.16 8.16E-05 4429 s at 8.33 5.28 3.87 1.12 2.16 1.40E-05 0806_sat 25.44 14.18 11.84 2.44 2.15 1.71E-06 12296_at 12.31 5.3 5.73 1.01 2.15 9.97E-09 18160 at 6.86 4.01 3.2 0.79 2.14 4.05E-06 04039_at 24.53 20.97 11.47 4.18 2.14 7.35E-04 0727 s at 10.36 3.6 4.84 1.76 2.14 4.97E-11 17814 at 7.72 3.52 3.62 0.94 2.13 4.02E-08 22037 at 2.89 2.29 1.36 0.48 2.13 3.35E-04 )2345 s at 11.17 9.71 5.24 1.46 2.13 8.72E-04 )3040 s at 9.22 5.83 4.33 1.21 2.13 1.63E-05 .6071 x at 5 2.12 2.36 0.93 2.12 1.11E-08 00812 at 13.81 8.47 6.51 1.74 2.12 1.07E-05 .01098 at 7.33 2.85 3.47 0.87 2.12 1.19E-09 02974 at 40.47 30.63 19.13 8.34 2.12 2.27E-04 .01577_at 22.25 10.65 10.53 2.35 2.11 1.31E-07 18686_s at 3.47 2.08 1.64 0.57 2.11 8.24E-06 18048 at 24.25 20.49 11.49 1.91 2.11 6.78E-04 01487 at 19.44 13.36 9.22 2.61 2.11 6.05E-05 03196 at 4.31 3.38 2.04 0.37 2.11 3.08E-04 10849 s at 7.11 2.53 3.38 1.05 2.11 1.31E-10 12694 s at 5.75 2.1 2.73 0.58 2.1 3.01E-10 [7799 x at 10.14 8.05 4.82 1.51 2.1 3.80E-04 39365 s at 4.11 2.34 1.96 0.67 2.1 3.90E-06 Z17988_at 20.17 12.11 9.6 2.24 2.1 8.48E-06 )3904 x at 10.53 4.75 5.02 1.36 2.1 4.53E-08 .00986 at 4.14 2.96 1.98 0.45 2.09 1.08E-04 101491 at 10.56 6.28 5.04 0.93 2.09 7.56E-06 01663 s at 13.53 7.67 6.47 1.32 2.09 3.51E-06 00942 s at 17.33 7.41 8.29 1.87 2.09 1.47E-08 00973 sat 6.78 3.14 3.24 1 2.09 8.67E-08 37943 x at 6.92 2.75 3.31 0.85 2.09 2.78E-09 18899 x at 5.47 2.2 2.62 0.72 2.09 3.61E-09 218966_at 6.94 4.57 3.33 0.9 2.08 3.83E-05 20240 s at 4.17 2.04 2 0.37 2.08 2.48E-07 09026 x at 51.78 25.3 24.89 3.87 2.08 2.53E-07 01403 s at 20.44 7.99 9.84 2.17 2.08 2.12E-09 13113 s at 9.36 3.13 4.51 1.6 2.08 3.53E-11 13971 _sat 4.56 2.5 2.2 0.4 2.07 2.33E-06 11769._x at 6.94 2.71 3.36 0.83 2.07 2.26E-09 01161 s at 37.5 30.34 18.13 12.68 2.07 8.21E-04 25 WO 2006/125195 PCT/US2006/019614 AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) 02990 at 13.28 9.72 6.42 1.69 2.07 1.72E-04 8418_sat 4.36 2.04 2.11 0.57 2.07 1.36E-07 2429 s at 8.94 5.13 4.33 1.15 2.06 5.39E-06 09215_at 8.81 5.52 4.27 1.62 2.06 2.44E-05 7949 s at 10.36 6.16 5.02 1.03 2.06 9.23E-06 16499 sat 6.14 2.26 2.98 0.72 2.06 5.40E-10 18027 at 9.33 4.24 4.53 0.87 2.06 7.08E-08 19479 at 2.19 1.8 1.07 0.25 2.06 6.63E-04 8880 sat 7.22 2.75 3.51 2.4 2.06 1.60E-08 5416_sat 11.83 4.07 5.76 1.05 2.06 1.08E-10 19559 at 8.42 3.14 4.11 1.03 2.05 9.10E-10 1342 x at 5.78 2.45 2.82 1.47 2.05 4.07E-08 17724 at 29.67 14.99 14.51 2.43 2.04 6.51E-07 12330 at 17.25 11.56 8.44 3.31 2.04 7.30E-05 08817 at 8.31 3.45 4.07 1.01 2.04 1.23E-08 04040 at 4.58 2.75 2.24 0.68 2.04 1.37E-05 13854 at 4.44 2.2 2.18 0.44 2.04 4.56E-07 )0729 s _at 27.19 8.63 13.33 3.33 2.04 1.28E-11 )1970 s at 11.22 8.6 5.51 1.74 2.04 3.64E-04 ,03021 at 6.06 4.66 2.98 0.99 2.03 3.92E-04 kFFX-r2 ;28SrRNA- 18.14 13.08 8.93 5.55 2.03 2.75E-04 3 at )0900_s at 4.92 2.85 2.42 0.62 2.03 8.48E-06 )3800 sat 7.31 3.68 3.6 0.78 2.03 7.24E-07 112320 at 40.81 19.46 20.16 3.1 2.02 2.59E-07 17892_s at 5.67 1.96 2.8 0.73 2.02 1.64E-10 118270_at 7.5 4.58 3.71 1.27 2.02 2.16E-05 !02567_at 18.58 9.97 9.2 1.65 2.02 2.37E-06 Z01302 at 10.89 6.47 5.4 1.68 2.02 1.45E-05 14113 s at 4.17 2.34 2.07 0.25 2.02 4.98E-06 )6438 x at 17.64 5.63 8.76 2.28 2.01 2.03E-11 00683 s at 7.25 5.94 3.6 0.91 2.01 8.19E-04 Z05505_at 3.67 2.22 1.82 0.39 2.01 1.77E-05 18055 s at 5.36 3.18 2.67 0.8 2.01 1.47E-05 09515 sat 12.72 8.41 6.33 1.72 2.01 6.79E-05 221831 at 4.64 3.22 2.31 1.2 2.01 1.72E-04 21942 s at 5.08 2.29 2.53 0.84 2.01 1.14E-07 213797_at 4.06 3.14 2.02 0.54 2.01 4.76E-04 09517 s at 12.19 4.74 6.09 1.16 2 4.18E-09 13330 s at 5.25 2.37 2.62 0.72 2 1.20E-07 13617_s at 7.56 2.86 3.78 0.9 2 2.38E-09 07314_x at 1.94 1.15 3.89 2.23 0.5 3.17E-06 19423 _x at 4.5 2.78 9 2.44 0.5 8.47E-11 26 WO 2006/125195 PCT/US2006/019614 AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) 5626 at 6.94 6.35 13.89 5.43 0.5 1.86E-06 11984 at 11.81 5.69 23.64 4.1 0.5 2.35E-15 03848 at 11.69 3.89 23.51 3.11 0.5 1.03E-22 0965 s _at 13.14 12.71 26.49 6.57 0.5 6.00E-07 01531_at 42.64 25.43 86.04 26.03 0.5 7.92E-11 7509 sat 2.58 0.84 5.24 3.63 0.49 1.67E-05 5022 s at 4.39 1.18 8.91 3.22 0.49 3.82E-12 7697_xat 7.31 5.71 14.84 2.95 0.49 3.04E-09 15019 s at 3.08 1.93 6.27 1.94 0.49 1.92E-10 0845 sat 20.53 13.56 41.8 19.39 0.49 1.37E-07 03341 at 6.44 2.21 13.13 3.38 0.49 6.80E-17 9657 sat 4.94 2.55 10.11 2.43 0.49 6.13E-14 20684_at 4.22 3.03 8.64 3.02 0.49 7.01E-09 03118 at 4.92 2.76 10.07 3.49 0.49 1.17E-10 1924 s at 13.08 10.83 26.82 17.51 0.49 4.60E-05 32032 at 6 1.99 12.31 3.01 0.49 5.45E-18 18878 s at 4.61 2.25 9.47 2.01 0.49 1.98E-15 ,12914_at 3.08 2.37 6.33 1.94 0.49 6.70E-09 104847 at 7.58 2.81 15.58 2.86 0.49 2.64E-20 .06110 at 4.11 3.5 8.47 4.73 0.49 8.63E-06 13587 s at 3.67 2.22 7.56 2.72 0.49 5.00E-10 ,03547_at 5.47 3.16 11.31 2.78 0.48 8.38E-13 114696 at 18.56 15.23 38.38 11.27 0.48 1.43E-08 120088 at 9.94 11.63 20.58 12.55 0.48 1.73E-04 )2724 sat 3.5 2.21 7.24 2.14 0.48 5.23E-11 )0788 sat 10.58 6.51 21.91 4.37 0.48 1.43E-12 )1393 sat 5.64 4.68 11.69 2.48 0.48 5.51E-09 113376 at 19.11 9.52 39.69 9.7 0.48 1.04E-14 )_4621 s at 6.89 5.44 14.31 4.68 0.48 1.11E-08 114945_at 2.58 1.65 5.38 2.79 0.48 3.42E-07 121757 at 11.92 8.24 24.82 5.78 0.48 5.42E-11 11985 sat 8.83 5.51 18.42 4.38 0.48 3.30E-12 00871 sat 114.36 92.98 239.29 39.36 0.48 1.63E-09 02842 s at 13.33 7.04 27.91 6.64 0.48 2.16E-14 219155_at 7.72 3.68 16.18 3.79 0.48 8.61E-16 203234_at 7.36 6.6 15.42 5.81 0.48 2.03E-07 01170 s at 24.28 14.69 50.93 13.42 0.48 2.42E-12 03973_sat 27.83 27.62 58.4 26.75 0.48 3.47E-06 219040_at 4.64 1.99 9.76 4.19 0.48 6.47E-10 214714 at 21.69 10.31 45.67 6.4 0.48 2.31E-17 219279 at 4.47 3.08 9.42 2.41 0.47 4.42E-11 40420_at 12.36 4.94 26.07 5.45 0.47 4.30E-19 214467 at 6.61 5.73 13.96 3.36 0.47 8.57E-09 27 WO 2006/125195 PCT/US2006/019614 Qualifier AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) 102518_at 8.14 3.49 17.2 3.07 0.47 4.27E-19 34224 s at 12.31 6.64 26.02 5.13 0.47 4.35E-15 103045 at 10.53 9.69 22.31 8.95 0.47 3.33E-07 39582 at 5.56 3.89 11.78 2.45 0.47 1.97E-11 10225 x at 3.22 3.17 6.84 2.38 0.47 3.53E-07 34891 sat 10.81 13.93 22.96 10.47 0.47 5.17E-05 18711 s at 2.67 0.93 5.67 2.06 0.47 1.60E-12 )4615 x at 16.78 6.89 35.67 7.66 0.47 9.15E-19 .09959 at 2.47 2.44 5.27 2.64 0.47 4.53E-06 )5254 x at 2.81 2.93 5.98 1.7 0.47 4.07E-07 04396 s at 3.5 2.52 7.47 1.78 0.47 4.98E-11 Z18319 at 20.83 13.47 44.58 8.71 0.47 8.34E-13 2-04369_at 4.14 1.96 8.87 2.55 0.47 1.47E-14 01662 s at 4.5 1.7 9.64 2.62 0.47 9.45E-17 12998 x at 13.08 9.49 28.04 10.7 0.47 3.46E-09 00921 s at 53.22 28.35 114.13 18.76 0.47 5.58E-16 04588 s at 18.61 20.76 39.91 12.4 0.47 1.36E-06 38881 x at 18.72 6.34 40.2 8.52 0.47 2.85E-21 202861 at 10.44 7.95 22.44 9.06 0.47 1.34E-08 02464 s at 11.58 10.18 24.91 10.44 0.46 1.50E-07 202388 at 76.19 54.29 164.22 41.31 0.46 2.71E-11 219118 at 4.44 2.69 9.62 4.28 0.46 4.33E-09 213906 at 3.03 3.32 6.56 2.78 0.46 2.86E-06 02880 s at 15.92 8.13 34.47 6.64 0.46 9.28E-17 01631 s at 17.97 23.34 38.98 25.56 0.46 2.35E-04 213758 at 4.75 2.56 10.31 2.75 0.46 1.89E-14 09616 s at 2.92 2.74 6.33 3.05 0.46 1.05E-06 05281 s at 3.75 1.95 8.18 1.66 0.46 1.44E-16 204215 at 9.06 5.19 19.76 5.5 0.46 1.33E-13 202478_at 5.25 5.33 11.51 3.92 0.46 1.68E-07 212812 at 5.5 4.01 12.07 4.32 0.46 6.01E-10 07826 s at 1.61 1.02 3.56 2.27 0.45 2.92E-06 218764 at 15.89 10.54 35.09 7.49 0.45 3.50E-13 202072 at 2.72 3.04 6.02 5.11 0.45 5.57E-04 210439 at 1.67 1.88 3.69 1.64 0.45 2.90E-06 203320_at 17.06 9.47 37.76 9.28 0.45 3.65E-15 204440 at 22 15.12 48.71 17.66 0.45 1.79E-10 11458 s at 18.22 12.73 40.36 14.48 0.45 1.95E-10 212769_at 4.28 2.43 9.49 3.85 0.45 1.48E-10 21841 s at 26.53 35.63 59.04 20.05 0.45 9.97E-06 217784 at 2.56 1.56 5.69 1.82 0.45 1.90E-12 02782 s at 5.61 2.91 12.56 3.79 0.45 2.24E-14 20987 s at 7.81 4.43 17.47 3.82 0.45 9.43E-16 28 WO 2006/125195 PCT/US2006/019614 AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) .18708_at 13.78 5.39 30.84 10.28 0.45 2.34E-14 15785 sat 7.61 5.25 17.04 6.85 0.45 6.95E-10 t02969 at 3.78 1.87 8.47 2.2 0.45 2.29E-16 )7000 s at 3.94 2.62 8.84 1.77 0.45 1.12E-13 )3146 s at 4.81 2.96 10.78 2.74 0.45 4.69E-14 103555 at 4.53 2.1 10.16 3.03 0.45 2.68E-15 )6130 s at 2 2.22 4.49 1.63 0.45 4.62E-07 )2928 s at 4.06 2.2 9.11 3.08 0.45 6.61E-13 )4627_sat 3.78 5.4 8.49 4.01 0.45 4.89E-05 109674 at 3.64 2.73 8.18 3 0.44 4.83E-10 10319 s at 12.56 7.6 28.22 13.99 0.44 1.37E-08 )4158_s at 10.03 6.08 22.56 10.29 0.44 2.24E-09 104731 at 3.86 3.47 8.69 3.62 0.44 3.88E-08 122315 at 1.83 1.13 4.13 2.07 0.44 1.83E-08 114617 at 12.61 16.66 28.44 15.51 0.44 3.89E-05 32284 s at 8.89 8.02 20.07 6.83 0.44 5.60E-09 11429 s at 42.89 42.53 96.87 27.37 0.44 1.47E-08 11919 s at 85.36 57.12 192.87 44.91 0.44 1.78E-13 112508 at 18.44 8.34 41.78 8.05 0.44 2.82E-20 D6472 s at 5.03 3.13 11.4 5.22 0.44 2.29E-09 D2761 s at 5.06 4.7 11.49 3.49 0.44 3.75E-09 10146 x at 4.69 4.33 10.69 3.95 0.44 1.22E-08 13193 x at 36.97 43.8 84.31 30.06 0.44 7.58E-07 215275 at 5.08 4.33 11.6 2.02 0.44 8.07E-11 205070 at 4.56 1.93 10.4 3.65 0.44 1.03E-13 20890 sat 21.25 7.85 48.53 8.16 0.44 6.68E-25 10606 x at 3.72 3.43 8.51 3.35 0.44 1.80E-08 204491_at 4.58 2.64 10.49 2.91 0.44 9.84E-15 220066 at 2.44 1.89 5.6 1.97 0.44 2.04E-10 218964 at 2.31 1.01 5.29 1.65 0.44 1.85E-15 04019 s at 8.22 7.92 18.87 8.96 0.44 2.32E-07 09688 s at 4.11 1.53 9.44 2.57 0.44 3.01E-18 212400 at 6.97 5.85 16.04 4.38 0.43 O1.01E-10 218032 at 13.33 6.46 30.69 6.13 0.43 1.76E-19 206337 at 5.06 4.79 11.64 4.48 0.43 1.76E-08 219947_at 4.83 4.12 11.18 4.36 0.43 2.91E-09 204912_at 21.56 15.35 49.89 11.11 0.43 2.36E-13 207840_at 2.94 1.82 6.84 2.87 0.43 1.34E-10 204951_at 13.06 8.97 30.44 9.01 0.43 6.62E-13 14049_x at 2.31 1.8 5.38 1.83 0.43 7.17E-11 18831 s at 7.81 7.89 18.22 5.55 0.43 7.63E-09 208450 at 9.64 12.41 22.51 14.98 0.43 6.30E-05 05992 sat 2.17 0.88 5.07 1.79 0.43 4.36E-14 29 WO 2006/125195 PCT/US2006/019614 uaier AML AML Disease-Free Disease-Free AML/ P-value qualifierr Average StDev Average StDev Disease-Free (unequal) ,06118 at 8.22 6.74 19.24 3.26 0.43 6.99E-12 18309 s at 4.44 3.19 10.42 2.62 0.43 2.89E-13 50084 at 3.33 1.62 7.82 1.77 0.43 4.04E-19 )2693 s at 12.33 8.89 29.04 8.01 0.42 5.79E-13 07460 at 2.5 1.48 5.89 1.82 0.42 3.62E-14 )4487 s at 3.58 2.76 8.44 1.91 0.42 1.07E-12 .7838 s at 10.67 10.49 25.22 8.21 0.42 3.55E-09 )2833 s at 26.31 29.07 62.33 20.13 0.42 3.54E-08 .0915 _xat 30.81 41.79 73.13 26.03 0.42 1.97E-06 12671 s at 16.78 17.19 39.93 22.25 0.42 1.10E-06 )7339_s at 17.11 21.69 40.8 17.23 0.42 1.22E-06 11724_s at 3.5 2.99 8.36 2.78 0.42 1.32E-10 11059 sat 31.17 21.47 74.56 15.03 0.42 6.90E-15 )9201_x at 75.19 49.33 179.91 39.06 0.42 1.63E-15 112501_at 86.17 73.18 206.33 47.17 0.42 8.81E-12 101739 at 23.75 24.43 56.96 26.6 0.42 1.15E-07 107072 at 4.08 3.15 9.82 4.27 0.42 9.05E-10 )0920 s at 35.61 25.77 85.78 35.09 0.42 1.24E-10 103334_at 3.61 1.95 8.71 2.18 0.41 9.88E-18 )4622 x at 18.31 17.05 44.18 16.48 0.41 1.60E-09 112231 at 4.17 2.13 10.07 2.21 0.41 1.45E-19 32968 s at 5.33 2.6 12.89 3.62 0.41 2.13E-17 )2637 s _at 9.5 6.86 23.02 8.76 0.41 2.23E-11 ,13539 at 19.25 20.53 46.69 18.53 0.41 2.78E-08 ,05291 at 9.94 6.68 24.13 9.38 0.41 1.22E-11 32723 s at 5.75 3.17 13.98 5.55 0.41 2.90E-12 36343 s at 1.39 0.77 3.38 1.63 0.41 5.98E-10 03543 s at 4.5 4.14 10.98 3.51 0.41 1.87E-10 02644 s at 59.19 51.04 144.44 34.17 0.41 5.67E-12 D9345 s at 7.08 6.23 17.29 3.22 0.41 6.62E-12 219622 at 10.28 8.75 25.09 9.02 0.41 1.13E-10 19528 sat 7.08 8.42 17.36 4.22 0.41 2.09E-08 117591 at 2.06 1.07 5.04 2.38 0.41 2.28E-10 11796 sat 27.44 38.15 67.36 21.64 0.41 8.01E-07 04838 s at 2.33 0.89 5.73 2.78 0.41 2.59E-10 213915_at 18.33 20.83 45.07 17.39 0.41 4.26E-08 16248_sat 20.22 17.84 49.91 17.47 0.41 1.04E-10 13142 x at 8.86 6.46 21.93 5.84 0.4 3.38E-14 203888 at 2.03 2.54 5.02 3.2 0.4 1.09E-05 11841 s at 2.5 2.08 6.2 1.56 0.4 1.02E-12 204118 at 62.5 46.31 155.16 22.34 0.4 9.75E-15 12841 s at 1.28 0.61 3.18 1.99 0.4 1.41E-07 05255_x at 16.17 14.85 40.62 15.77 0.4 4.07E-10 30 WO 2006/125195 PCT/US2006/019614 AML AML Disease-Free Disease-Free AML/ P-value ualifier Average StDev Average StDev Disease-Free (unequal) 871 s at 1.92 1.89 4.82 2.07 0.4 4.73E-09 601 s_at 2.03 1.66 5.11 2.05 0.4 9.10E-11 8454_at 22.08 29.37 55.98 18.38 0.39 1.30E-07 536 s at 5.33 2.99 13.53 4.6 0.39 6.76E-15 13708 at 15.56 14.78 39.62 11.95 0.39 3.49E-11 !048 s at 6.08 3.87 15.51 4.48 0.39 5.89E-16 3078 s at 19.14 16.05 49.02 13.66 0.39 4.77E-13 )9447_at 3.42 3.02 8.76 2.33 0.39 1.51E-12 L2313_at 5.28 3.91 13.56 3.61 0.39 6.79E-15 3205 s at 20.5 7.16 53.16 16.23 0.39 4.03E-18 )824 s at 5.67 4.17 14.82 5.23 0.38 2.79E-13 13958 at 16.64 18.55 43.58 12.27 0.38 4.17E-10 1558 s at 8.64 9.5 22.76 8.03 0.38 8.56E-10 7911 s at 3.67 2.54 9.69 2.02 0.38 1.48E-17 8622 s at 15.17 10.19 40.31 11.92 0.38 4.22E-16 18345 at 5.08 5.64 13.53 8.52 0.38 9.04E-07 4777 s_at 6.61 6.7 17.62 7.23 0.38 5.40E-10 13300 at 7.72 3.86 20.64 11.03 0.37 9.54E-10 10054 at 8.53 5.57 22.8 5.3 0.37 1.89E-18 9117 s at 13.44 13.14 36 14.7 0.37 2.29E-10 4244 s at 5.5 3.33 14.73 4.12 0.37 6.56E-18 0253 _at 21.03 10.29 56.42 18.7 0.37 1.19E-16 22142 at 3.25 1.63 8.73 2 0.37 2.29E-22 05241_at 7 5.53 18.93 7.57 0.37 3.84E-12 02320 at 2.08 0.87 5.64 3.27 0.37 5.08E-09 04103 at 4.97 5.31 13.51 14.8 0.37 6.82E-04 16881 s at 2.25 1.66 6.13 3.42 0.37 5.33E-09 12956 at 2.14 1.15 5.84 2.27 0.37 3.58E-14 1583 x at 1.53 0.77 4.18 1.74 0.37 3.06E-13 .1962_s at 9.39 6.99 25.69 6.67 0.37 1.52E-16 04411 _at 1.78 1.24 4.87 2.01 0.37 1.46E-12 )8657 s at 3.61 2.39 9.91 2.33 0.36 6.92E-19 119593_at 4.25 4.62 11.71 3.75 0.36 4.65E-11 2150 s at 6.83 4.88 19 6.51 0.36 6.54E-15 101425 at 12.89 13.33 35.84 8.67 0.36 1.85E-12 )1565 sat 28.14 20.24 78.27 22.51 0.36 1.22E-16 )2643 s at 24.31 20.55 67.76 21.16 0.36 3.10E-14 09501 _at 6.56 3.79 18.38 4.61 0.36 1.08E-20 121890_at 2.44 1.42 6.87 3.41 0.36 6.50E-11 32295 s at 16.17 14.15 45.93 10.89 0.35 2.00E-15 Z01341 at 6.69 7.59 19.07 7.92 0.35 4.50E-10 11840 s at 2.28 1.37 6.49 2.41 0.35 4.46E-15 218486 at 6.61 3.84 18.89 4.38 0.35 5.27E-22 31 WO 2006/125195 PCT/US2006/019614 AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) 212196_at 8.97 6.51 25.67 6.11 0.35 1.52E-18 219359 at 5.64 4.62 16.31 6.72 0.35 1.37E-12 204655 at 11.97 13.9 34.98 16.75 0.34 2.21E-09 06366 x at 2.03 2.63 5.93 3.3 0.34 7.78E-08 14146 s at 30.83 37.74 90.76 32.92 0.34 1.46E-10 38037 at 6.39 8.63 18.84 10.71 0.34 1.33E-07 09062 x at 4.06 2.67 12.07 2.98 0.34 9.87E-21 13524 s at 33.97 35.69 101.51 48.5 0.33 2.99E-10 213135 at 5 4.5 15.02 3.44 0.33 1.80E-16 02524 s at 13.56 11.11 40.89 10.45 0.33 1.10E-17 10479 s at 3.94 3.3 11.96 3.57 0.33 1.86E-16 210279 at 4.28 5.27 13.02 7.35 0.33 2.25E-08 1405 i at 11.69 15.87 35.67 15.86 0.33 2.64E-09 04198 s at 12.08 10.51 37 14.46 0.33 1.17E-13 01566 x at 5.64 4.5 17.31 6.7 0.33 2.67E-14 04197 s at 19.69 17.33 60.64 15.02 0.32 3.00E-17 18793 s at 2.03 1.16 6.24 2 0.32 1.17E-18 209728 at 11.25 18.4 34.69 35.17 0.32 2.53E-04 202206 at 14.14 12.67 43.8 14.09 0.32 1.53E-15 213624 at 2.19 2.74 6.82 3.37 0.32 1.74E-09 218696 at 6.86 4.13 21.42 5.15 0.32 2.48E-23 212195 at 8.11 7.38 25.33 6.15 0.32 3.87E-17 06296 x at 2.86 1.71 8.96 4.89 0.32 1.58E-10 01189 s at 2.94 2.91 9.31 2.22 0.32 3.76E-16 219099 at 3.78 2.51 11.96 3.3 0.32 1.10E-20 12187 x at 4.03 2.93 12.91 6.52 0.31 1.65E-11 09604_sat 7.36 6.16 23.6 7.61 0.31 7.32E-17 204794 at 7.64 7.51 24.51 7.87 0.31 3.14E-15 10113 s at 3.61 2.61 11.64 3.86 0.31 9.95E-18 204790 at 2.81 1.51 9.07 4.45 0.31 3.37E-12 02208 s at 8.67 8.45 28.07 13.73 0.31 2.85E-11 203821 at 11.81 15.7 38.84 20.42 0.3 2.38E-09 14567 s at 1.39 0.9 4.58 2.31 0.3 7.72E-12 03887 s at 4.28 5.84 14.13 9.37 0.3 1.57E-07 06655 s at 2.36 1.64 7.82 4.21 0.3 5.47E-11 14219 xat 2 1.41 6.78 3.91 0.3 2.94E-10 204793 at 4.81 4.69 16.31 3.6 0.29 2.70E-18 214470 at 18.14 17.22 61.67 18.24 0.29 1.86E-17 202207 at 20.22 16.82 69.47 14.62 0.29 9.60E-22 02988 s at 2.58 1.54 8.89 8.21 0.29 6.99E-06 11748_x at 5.36 3.94 18.47 10.14 0.29 6.29E-11 210164 at 8.28 10.61 28.6 12.55 0.29 1.45E-11 221756 at 13.81 11.17 47.98 13.2 0.29 1.38E-20 32 WO 2006/125195 PCT/US2006/019614 AML AML Disease-Free Disease-Free AML/ P-value Qualifier Average StDev Average StDev Disease-Free (unequal) 08146 s at 10.75 9.07 38.51 13.32 0.28 1.04E-17 36390 x at 16.11 23.68 58.53 25.43 0.28 3.02E-11 214032 at 4.78 4.92 17.49 6.3 0.27 4.56E-16 216834 at 10.5 11.27 38.56 28.38 0.27 9.67E-08 10426 x at 4.17 3.96 15.78 4.91 0.26 4.55E-19 20646 sat 4.36 5.93 17.51 6.99 0.25 4.98E-14 203414 at 7.78 5.11 31.47 7.37 0.25 5.84E-28 10512 s at 3 2.33 12.18 7.16 0.25 6.16E-11 03271 s at 1.58 0.91 6.6 2.19 0.24 1.08E-20 204081_at 7.83 4.77 32.69 13.35 0.24 1.14E-16 204115 at 2.75 2.76 11.8 5 0.23 8.80E-16 37145_at 14.22 22.96 62.47 30.08 0.23 3.86E-12 05495 s at 12.86 19.7 57.69 30.42 0.22 1.07E-11 205237_at 29.56 38.91 132.64 44.91 0.22 1.12E-17 210031 at 11.72 12.49 53.98 16.51 0.22 1.72E-21 20532 s at 3 3.88 14.02 12.01 0.21 3.51E-07 21211 s at 2.44 1.08 11.93 5.59 0.2 6.63E-15 201506 at 6.56 9.19 47.31 12.83 0.14 2.13E-27 Table 2. Annotation of Genes Differentially Expressed in AML vs. Disease-Free PBMCs ?ualifier Gene Symbol Gene Name Unigene No. Accession No. 3948 sat MPO myeloperoxidase Hs.1817 J02694 03949 at MPO myeloperoxidase Hs.1817 NM 000250 06310 at SPINK2 serine protease inhibitor, Kazal type, 2 Hs.98243 NM_021114 - (acrosin-trypsin inhibitor) 09905 at HOXA9 homeo boxA9 Hs.127428 AI246769 4575 s at AZU1 azurocidin 1 (cationic antimicrobial protein Hs.72885 NM 001700 - _ -37) 06871_at ELA2 elastase 2, neutrophil Hs.99863 NM_001972 4651 s at HOXA9 homeo boxA9 Hs.127428 U41813 0084 x at TPS1, TPSB1 tryptase beta 1, tryptase, alpha Hs.347933 AF206665 5683 x at TPS1, TPSB1, tryptase beta 1, tryptase beta 2, tryptase, Hs.347933 NM 003294 S- TPSB2 alpha 04798 at MYB v-myb myeloblastosis viral oncogene Hs.1334 NM_005375 - homolog (avian) 7023 xat TPSB1, TPSB2 tryptase beta 1, tryptase beta 2 Hs.294158, AF099143 Hs.347933 6474 x at TPSBI, TPSB2 tryptase beta 1, tryptase beta 2 Hs.347933 AF206667 02016 at MEST mesoderm specific transcript homolog Hs.79284 NM 002402 0201_ atMS (mouse) 7134 x at TPS1, TPSBI1, tryptase beta 1, tryptase beta 2, tryptase, Hs.294158 NM 024164 S TPSB2 alpha 5382 x at TPS1, TPSB1 tryptase beta 1, tryptase, alpha Hs.347933 AF206666 15950 s at CAl carbonic anhydrase I Hs.23118 NM 001738 15051 sat KIT v-kit Hardy-Zuckerman 4 feline sarcoma Hs.81665 NM 000222 _505_____ KIT____viral oncogene homolog 33 WO 2006/125195 PCT/US2006/019614 )ualifier Gene Symbol Gene Name Unigene No. Accession No. 1709 s at SCGF stem cell growth factor; lymphocyte Hs.105927 BC005810 secreted C-type lectin 5131 x at SCGF stem cell growth factor; lymphocyte Hs.105927 NM 002975 secreted C-type lectin 19054 at FLJ14054 hypothetical protein FLJ14054 Hs.13528 NM_024563 4304 s at PROML1 prominin-like 1 (mouse) Hs.112360 NM_006017 36674 at FLT3 fmns-related tyrosine kinase 3 Hs.385 NM 004119 7741_xat TPS1 tryptase, alpha Hs.334455 NM_003293 32589 at TYMS thymidylate synthetase Hs.82962 NM_001071 D783 x at SCGF stem cell growth factor; lymphocyte Hs.105927 D86586 secreted C-type lectin 1922 s at CAT catalase Hs.76359 AY028632 1427 s at SEPP1 selenoprotein P, plasma, 1 Hs.3314 NM_005410 D6111 at RNASE2 ribonuclease, RNase A family, 2 (liver, Hs.728 NM_002934 - eosinophil-derived neurotoxin) 2503 s at KIAA0101 KIAA0101 gene product Hs.81892 NM014736 20377 at HSPCO53 HSPC053 protein Hs.128155 NM_014151 1310 sat P311 P311 protein Hs.142827 NM_004772 19672 at ERAF erythroid associated factor Hs.274309 NM_016633 05624 at CPA3 carboxypeptidase A3 (mast cell) Hs.646 NM_001870 05609 at ANGPTI angiopoietin 1 Hs.2463 NM_001146 06834 at HBD hemoglobin, delta Hs.36977 NM_000519 01162 at IGFBP7 insulin-like growth factor binding protein 7 Hs.119206 NM_001553 01432 at CAT catalase Hs.76359 NM_001752 4430 s at SLC2A5 solute carrier family 2 (facilitated Hs.33084 NM_003039 glucose/fructose transporter), member 5 20416 at KIAA1939 KIAA1939 protein Hs.182738 NM_024837 proteoglycan 2, bone marrow (natural killer 1743 s at PRG2 cell activator, eosinophil granule major Hs.99962 BC005929 basic protein) Meisl, myeloid ecotropic viral integration 01416_at MEIS3, SOX4 site 1 homolog 3 (mouse), SRY (sex Hs.83484 BG528420 determining region Y)-box 4 13150 at HOXA10 homeo box A10 Hs.110637 BF792917 9543 sat CD34, FLJ00005 CD34 antigen, FLJ00005 protein Hs.367690 M81104 13258 at Hs.288582 BF511231 0664 s at TFPI tissue factor pathway inhibitor (lipoprotein- Hs.170279 AF021834 associated coagulation inhibitor) 6067 s at WT1 Wilms tumor 1 Hs. 1145 NM_024426 '9757 s at MYCN v-myc myelocytomatosis viral related Hs.25960 BC002712 _9757___._at MYNoncogene, neuroblastoma derived (avian) Hs.25960 BC002712 3515 x at GARS, HBG1, glycyl-tRNA synthetase, hemoglobin, Hs.283108 AI133353 - -HBG2 gamma A, hemoglobin, gamma G 9837 sat C17 cytokine-like protein C17 Hs.13872 NM_018659 8899_s at BAALC brain and acute leukemia, cytoplasmic Hs.169395 NM_024812 10665_at TFPI tissue factor pathway inhibitor (lipoprotein- Hs.170279 AFO21834 associated coagulation inhibitor) 06478 at KIAA0125 KIAA0125 gene product Hs.38365 NM_014792 1825 s_at LOC51097 CGI-49 protein Hs.238126 AL572542 02441_at KEO4 similar to Caenorhabditis elegans protein Hs.285818 AL568449 0_ a_ KEO4_C42C 1.9 34 WO 2006/125195 PCT/US2006/019614 Qualifier Gene Symbol Gene Name Unigene No. Accession No. aldo-keto reductase family 1, member C3 )9160_at AKR1C3 (3-alpha hydroxysteroid dehydrogenase, Hs.78183 AB018580 type II) 9788 s at FLJ21080 hypothetical protein FLJ21080 Hs.8109 NM 022743 19551 at BMO40 uncharacterized bone marrow protein Hs.26892 NM_018456 1955l BM04BM040 1163 s at IGFBP7 insulin-like growth factor binding protein 7 Hs.119206 NM_001553 419 x at GARS, HBG1, glycyl-tRNA synthetase, hemoglobin, Hs.283108 NM 000184 4__ HBG2 gamma A, hemoglobin, gamma G 39710_at MGC2306 hypothetical protein MGC2306 Hs.760 AL563460 31307 at FLJ10849 hypothetical protein FLJ10849 Hs.8768 AL534972 13147_at HOXAO10 homeo box A10 Hs.110637 AI375919 33675_at NUCB2 nucleobindin 2 Hs.3164 NM_005013 1004 s at ITM3 integral membrane protein 3 Hs.111577 NM_030926 4848 x at HBG1, HBG2 hemoglobin, gamma A, hemoglobin, Hs.266959 NM 000559 gamma G 5366 s at HOXB6 homeo boxB6 Hs.98428 NM_018952 02252 at RAB13 RAB13, member RAS oncogene family Hs.151536 NM_002870 3110 s at COL4A5 collagen, type IV, alpha 5 (Alport Hs.169825 AW052179 Ss syndrome) 19654 at PTPLA protein tyrosine phosphatase-like (proline Hs.114062 NM 014241 1__ t_ PTPAinstead of catalytic arginine), member a 8280 x at H2AFO H2A histone family, member O Hs.795 NM 003516 20232 at FLJ21032 hypothetical protein FLJ21032 Hs.247474 NM_024906 01324_at EMP1 epithelial membrane protein 1 Hs.79368 NM 001423 1892 s at IMPDH2 IMP (inosine monophosphate) Hs.75432 NM 000884 1_ s_ IMPDH2 _ dehydrogenase 2 18718 at PDGFC platelet derived growth factor C Hs.43080 NM 016205 09398 at HIF2 H1 histone family, member 2 Hs.7644 BC002649 01417_at AL136179 01459 at RUVBL2 RuvB-like 2 (E. coli) Hs.6455 NM_006666 UDP-N-acetyl-alpha-D 8313 s at GALNT7 galactosamine:polypeptide N- Hs.246315 NM 017423 acetylgalactosaminyltransferase 7 (GalNAc T7) 7459 x at GYPA, GYPB glycophorin A (includes MN blood group), Hs.343871 NM_002100 glycophorin B (includes Ss blood group) 4407 x at GYPA,GYPB glycophorin A (includes MN blood group), Hs.108694 AI240545 glycophorin B (includes Ss blood group) 02502 at ACADM acyl-Coenzyme A dehydrogenase, C-4 to C- Hs.79158 NM 000016 12 straight chain Meisl, myeloid ecotropic viral integration 1418 s at MEIS3, SOX4 site I homolog 3 (mouse), SRY (sex Hs.83484 NM 003107 determining region Y)-box 4 .4290_s at H2AFO H2A histone family, member O Hs.795 AI313324 )9790 s at CASP6 caspase 6, apoptosis-related cysteine Hs.3280 BC000305 protease .04069 at MEISI Meisl, myeloid ecotropic viral integration Hs.170177 NM_002398 0 site 1 homolog (mouse) 03502 at BPGM 2,3-bisphosphoglycerate mutase Hs.198365 NM 001724 19813_x_at TRG@ T cell receptor gamma locus Hs.112259 M16768 19218 at FLJ23058 hypothetical protein FLJ23058 Hs.98968 NM 024696 )2444 sat KEO4 similar to Caenorhabditis elegans protein Hs.285818 NM_006459 35 WO 2006/125195 PCT/US2006/019614 Qualifier Gene Symbol Gene Name Unigene No. Accession No. C42C1.9 01193 at IDH1 isocitrate dehydrogenase 1 (NADP+), Hs.11223 NM005896 - soluble _ 059 2175 s at AK2 adenylate kinase 2 Hs.171811 AL513611 phosphoribosylaminoimidazole 1013 s at PAICS carboxylase, Hs.117950 AA902652 103sa Pphosphoribosylaminoimidazole succinocarboxamide synthetase 05769 at FACVL1 fatty-acid-Coenzyme A ligase, very long- Hs. 11729 NM 003645 chain 1 08680 at PRDX1 peroxiredoxin 1 Hs.180909 L19184 12141 at MCM4 MCM4 minichromosome maintenance Hs.154443 AA604621 deficient 4 (S. cerevisiae) 3541 s at ERG v-ets erythroblastosis virus E26 oncogene Hs.45514 AI351043 like (avian) 2036 s at MCM4 MCM4 minichromosome maintenance Hs.154443 AI859865 deficient 4 (S. cerevisiae) 0668 s at DNMT3B DNA (cytosine-5-)-methyltransferase 3 beta Hs.251673 NM 006892 18847 at IMP-2 IGF-II mRNA-binding protein 2 Hs.30299 NM_006548 7294_s at ENO1 enolase 1, (alpha) Hs.254105 U88968 5215 s at LOC81691 exonucleaseNEF-sp Hs.177926 AC004381 13779_at LOC129080 putative emul Hs.289106 AL031186 18825 at LOC51162 NEUI protein Hs.91481 NM_016215 2009 s at STIP1 stress-induced-phosphoprotein 1 Hs.75612 AL553320 -__ at___ -STIP1__(Hsp70/Hsp90-organizing protein) 15996_s at AK2 adenylate kinase 2 Hs.171811 NM_013411 18729_at LXN latexin protein Hs.109276 NM_020169 19930 s at NFE2 nuclear factor (erythroid-derived 2), 45kD Hs.75643 L13974 18858 at FLJ12428 hypothetical protein FLJ12428 Hs.87729 NM_022783 6153 x at RECK reversion-inducing-cysteine-rich protein Hs.29640 AK022897 with kazal motifs 14409 s at EIF1AY eukaryotic translation initiation factor 1A, Hs.155103 BC005248 Y chromosome 05202 at PCMT1 protein-L-isoaspartate (D-aspartate) O- Hs.79137 NM 005389 - methyltransferase 15382 s at DF D component of complement (adipsin) Hs.155597 NM_001928 6920 s-at TRG@ T cell receptor gamma locus Hs. 112259 M27331 guanine nucleotide binding protein (G 09576_at GNAI1 protein), alpha inhibiting activity Hs.203862 AL049933 polypeptide 1 12246 sat CDK4 cyclin-dependent kinase 4 Hs.95577 NM_000075 12115_at FLJ13092 hypothetical protein FLJ13092 Hs.172035 AK023154 04168_at MGST2 microsomal glutathione S-transferase 2 Hs.81874 NM_002413 1820 x at GYPA glycophorin A (includes MN blood group) Hs.108694 U00179 5806_x at TRGC2 T cell receptor gamma constant 2 Hs.274509 M13231 15768 s at FACVLI fatty-acid-Coenzyme A ligase, very long- Hs.11729 NM 003645 -_ -chain 1 0829_s at SSBP2 single-stranded DNA binding protein 2 Hs.169833 AF077048 '8107 s at LOC81691 exonuclease NEF-sp Hs.177926 NM 030941 00923 at LGALS3BP lectin, galactoside-binding, soluble, 3 -_______ __binding protein Hs.79339 NM_005567 13116_s _at FECH ferrochelatase (protoporphyria) Hs.26 NM_000140 36 WO 2006/125195 PCT/US2006/019614 Qualifier Gene Symbol Gene Name Unigene No. Accession No. '4900_x at SAP30 sin3-associated polypeptide, 30kD Hs.20985 NM_003864 12845 sat RALBP1 ralA binding protein 1 Hs.75447 NM 006788 03787_at SSBP2 single-stranded DNA binding protein 2 Hs.169833 NM_012446 14170 sat CKS2 CDC28 protein kinase 2 Hs.83758 NM_001827 01413_at HSD17B4 hydroxysteroid (17-beta) dehydrogenase 4 Hs.75441 NM_000414 01054 at HNRPA0 heterogeneous nuclear ribonucleoprotein Hs.77492 BE966599 -_ _ 2AO 01952_at ALCAM activated leucocyte cell adhesion molecule Hs. 10247 AA156721 04647_at HOMER-3 Homer, neuronal immediate early gene, 3 Hs.166146 NM 004838 ,09892 at FUT4 fucosyltransferase 4 (alpha (1,3) Hs.2173 AF305083 2 fucosyltransferase, myeloid-specific) natriuretic peptide receptor C/guanylate 19789_at NPR3 cyclase C (atrionatriuretic peptide receptor Hs. 123655 AI628360 C) 12946 s at BTBD3 BTB (POZ) domain containing 3 Hs.7935 NM_014962 04011 at SPRY2 sprouty homolog 2 (Drosophila) Hs.18676 NM 005842 4909 s at DDAH2 dimethylarginine dimethylaminohydrolase 2 Hs.247362 AK026191 4391 xat TIF1 transcriptional intermediary factor 1 Hs.183858 NM 015905 13035 at KIAA0379 KIAA0379 protein Hs.32556 AI081194 4657 sat MEN1 multiple endocrine neoplasia I Hs.240443 AU134977 0613_s at SYNGR1 synaptogyrin 1 Hs.6139 BC000731 10615 s at AP2B 1 adaptor-related protein complex 2, beta 1 Hs.74626 AL567295 -_ -subunit 5537 x at DDAH2 dimethylarginine dimethylaminohydrolase 2 Hs.247362 AJ012008 06480_at LTC4S leukotriene C4 synthase Hs.456 NM_000897 2067 x at H2BFB H2B histone family, member B Hs.180779 AL353759 04173_at MLC1ISA myosin light chain 1 slow a Hs.90318 NM_002475 12268 at SERPINB1 serine (or cysteine) proteinase inhibitor, Hs.183583 NM 030666 Sclade B (ovalbumin), member 1I '1309 x at P311 P311 protein Hs.142827 U36189 5182 x at Hs.274511 AL050122 01037_at PFKP phosphofructokinase, platelet Hs.99910 NM_002627 14236 at Hs.172405 AA166684 0644 s at LAIRI leukocyte-associated Ig-like receptor 1 Hs.115808 AF109683 6323 x at OPHN1 oligophrenin 1 Hs.128824 NM_002547 01563 at SORD sorbitol dehydrogenase Hs.878 L29008 3301 xat TIF1 transcriptional intermediary factor 1 Hs.183858 AL538264 18039_at ANKT nucleolar protein ANKT Hs.279905 NM 016359 12174_at AK2 adenylate kinase 2 Hs.171811 W02312 18069 at MGC5627 hypothetical protein MGC5627 Hs.237971 NM_024096 6202 s at SPTLC2 serine palmitoyltransferase, long chain base Hs.59403 U15555 - -subunit 2 phosphoribosylaminoimidazole 11014 s at PAICS carboxylase, Hs.117950 NM 006452 phosphoribosylaminoimidazole Hs.117950 NM_006452 succinocarboxamide synthetase 2564_xat ARL2 ADP-ribosylation factor-like 2 Hs.154162 NM_001667 13588 s at TFDP2 transcription factor Dp-2 (E2F dimerization Hs.19131 BG034328 _3588__s _at _TFDP2 _ partner 2) H.93 B04 37 WO 2006/125195 PCT/US2006/019614 Qualifier Gene Symbol Gene Name Unigene No. Accession No. )8864 sat TXN thioredoxin Hs.76136 AF313911 [8883 s at FLJ23468 hypothetical protein FLJ23468 Hs.38178 NM 024629 15489 x at HOMER-3 Homer, neuronal immediate early gene, 3 Hs.166146 AI871287 )9360 s at RUNX1 runt-related transcription factor 1 (acute Hs.129914 D43968 myeloid leukemia 1; amll oncogene) 101503_at G3BP Ras-GTPase-activating protein SH3- Hs.220689 BG500067 domain-binding protein glucan (1,4-alpha-), branching enzyme 1 03282_at GBE1 (glycogen branching enzyme, Andersen Hs.1691 NM 000158 disease, glycogen storage disease type IV) )0696_s at GSN gelsolin (amyloidosis, Finnish type) Hs.290070 NM_000177 17869 at HSD17B12 hydroxysteroid (17-beta) dehydrogenase 12 Hs.279617 NM_016142 18579 x at H2B/S, H2BFS H2B histone family, member S, histone Hs.367748 NM_017445 family member [3129 s at GCSH glycine cleavage system protein H Hs.356054 AI970157 (aminomethyl carrier) 8342_s at FLJ23309 hypothetical protein FLJ23309 Hs.87128 NM 024896 )4026 s at ZWINT ZW10 interactor Hs.42650 NM_007057 )9825 s at UMPK uridine monophosphate kinase Hs.75939 BC002906 19179 s at LENG4 leukocyte receptor cluster (LRC) member 4 Hs.78768 BC003164 17975_at LOC51186 pp21 homolog Hs.15984 NM 016303 pyrroline-5-carboxylate synthetase 7791 s at PYCS (glutamate gamma-semialdehyde Hs. 114366 NM_002860 synthetase) )8967_sat AK2 adenylate kinase 2 Hs.171811 U39945 02371_at FLJ21174 hypothetical protein FLJ21174 Hs.194329 NM_024863 12055 at DKFZP586M1523 DKFZP586M1523 protein Hs.22981 BF689173 00703_at PIN dynein, cytoplasmic, light polypeptide Hs.5120 NM_003746 2262 x at DDAH2 dimethylarginine dimethylaminohydrolase 2 Hs.247362 NM_013974 MADS box transcription enhancer factor 2, 09200_at MEF2C polypeptide C (myocyte enhancer factor Hs.78995 AL536517 2C) 3572 s at SERPINB1 serine (or cysteine) proteinase inhibitor, Hs.183583 AI554300 clade B (ovalbumin), member I 0762 s at DLC1 deleted in liver cancer 1 Hs.8700 AF026219 0658 s at PHB prohibitin Hs.75323 AL560017 0999 s at GRB10 growth factor receptor-bound protein 10 Hs.81875 U66065 cytidine monophosphate-N 5518_sat CMAH acetylneuraminic acid hydroxylase (CMP- Hs.24697 NM_003570 N-acetylneuraminate monooxygenase) 17809_at HSPCO28 HSPCO28 protein Hs.5216 NM 014038 0725_x at FLJ23558 hypothetical protein FLJ23558 Hs.288552 NM 025095 8857 s at PCMT1 protein-L-isoaspartate (D-aspartate) O- Hs.79137 M93008 methyltransferase M.93M30 10401_at P2RX1 purinergic receptor P2X, ligand-gated ion Hs.41735 U45448 channel, 1 s.13U44 01555 at MCM3 MCM3 minichromosome maintenance Hs.179565 NM 002388 deficient 3 (S. cerevisiae) s.75 2708 s at H2BFQ H2B histone family, member Q Hs.2178 NM_003528 1826 s at LOC51097 CGI-49 protein Hs.238126 NM_016002 1684 s_ at DNCI2 dynein, cytoplasmic, intermediate Hs.66881 AF250307 polypeptide 2 38 WO 2006/125195 PCT/US2006/019614 ualifier Gene Symbol Gene Name Unigene No. Accession No. 1951 at ALCAM activated leucocyte cell adhesion molecule Hs.10247 BF242905 1564 s at SNL singed-like (fascin homolog, sea urchin) Hs.118400 NM003088 (Drosophila) 1897 s at CKS1 CDC28 protein kinase 1 Hs.348669 NM_001826 3395 at MLC1 megalencephalic leukoencephalopathy with Hs.74518 AL022327 at MLC subcortical cysts 1 1690 s at PDLIM1 PDZ and LIM domain 1 (elfin) Hs.75807 BC000915 )4565 at HT012 uncharacterized hypothalamus protein Hs.9676 NM 018473 HT012 1015 s at JUP junction plakoglobin Hs.2340 NM_021991 )9409_at GRB10 growth factor receptor-bound protein 10 Hs.81875 D86962 1490_xat H2BFG H2B histone family, member G Hs.182137 NM 003522 )3560 at GGH gamma-glutamyl hydrolase (conjugase, Hs.78619 NM 003878 )3560______~ atfolylpolygammaglutamyl hydrolase) s.81 _ 03 [3170 at CL683 weakly similar to glutathione peroxidase 2 Hs.43728 AA406605 )5227_at IL1RAP interleukin 1 receptor accessory protein Hs.173880 NM_002182 3927 s at C4S-2 chondroitin 4-O-sulfotransferase 2 Hs.25204 NM_018641 )318_xat PLAGL1 pleiomorphic adenoma gene-like 1 Hs.75825 BG547855 3783 s at STMN1 stathmin 1/oncoprotein 18 Hs.250811 NM_005563 13346_at LOC93081 hypothetical protein BC015148 Hs.13413 BE748563 )5418 at FES feline sarcoma oncogene Hs.7636 NM_002005 2107 s at MCM2 MCM2 minichromosome maintenance Hs.57101 NM_004526 deficient 2, mitotin (S. cerevisiae) )4082 at PBX3 pre-B-cell leukemia transcription factor 3 Hs.294101 NM_006195 32862 at FAH fumarylacetoacetate hydrolase Hs.73875 NM_000137 -_ (fumarylacetoacetase) 12526 at KIAAO610 KIAAO610 protein Hs.118087 AK002207 3358 x at GATA2, MGC2306 GATA binding protein 2, hypothetical Hs.760 BC002557 protein MGC2306 0615 s at FLJ10462 hypothetical protein FLJ10462 Hs.100895 NM_018099 31938 at CDK2API CDK2-associated protein 1 Hs.3436 NM_004642 D1202 at PCNA proliferating cell nuclear antigen Hs.78996 NM_002592 0648 s at GLUL glutamate-ammonia ligase (glutamine Hs.170171 NM_002065 synthase) 1277 s at HNRPAB heterogeneous nuclear ribonucleoprotein Hs.81361 NM 004499 A/B 0044 s at LYL1 lymphoblastic leukemia derived sequence 1 Hs.46446 BC002796 4501 s at H2AFY H2A histone family, member Y Hs.75258 AF044286 06589 at GFI1 growth factor independent 1 Hs.73172 NM_005263 1240_s at KIAA0102 KIAA0102 gene product Hs.77665 NM 014752 8626 s at VATI vesicle amine transport protein 1 Hs.157236 BC001913 05349 at GNAl5 guanine nucleotide binding protein (G Hs.73797 NM002068 protein), alpha 15 (Gq class) s. 97M00 6833 x at GYPB, GYPE glycophorin B (includes Ss blood group), Hs.372513 U05255 glycophorin E 16609 at Hs.336933 AF065241 18026 at HSPC009 HSPC009 protein Hs.16059 NM_014019 1464 x at CASP6 caspase 6, apoptosis-related cysteine Hs.3280 U20537 - -protease 8677 s at BSG basigin (OK blood group) Hs.74631 AL550657 6981 _x at SPN sialophorin (gpL1l5, leukosialin, CD43) Hs.80738 X60502 39 WO 2006/125195 PCT/US2006/019614 ualifier Gene Symbol Gene Name Unigene No. Accession No. 03744 at HMG4 high-mobility group (nonhistone Hs.19114 NM 005342 - chromosomal) protein 4 18461_at LOC51184 protein x 0004 Hs.284164 NM_016301 )1036_s_ at HADHSC L-3-hydroxyacyl-Coenzyme A Hs.8110 NM 005327 dehydrogenase, short chain 15600 x at HOXB5 homeo box B5 Hs.22554 A1052747 )7002 s at PLAGL1 pleiomorphic adenoma gene-like 1 Hs.75825 NM_002656 1713_x at KIAA0101 KIAA0101 gene product Hs.81892 BC005832 )8818_sat COMT catechol-O-methyltransferase Hs.240013 BC000419 19007 at FLJ13287 hypothetical protein FLJ13287 Hs.53263 NM_024647 01619_at PRDX3 peroxiredoxin 3 Hs.75454 NM_006793 )1231 sat ENO1 enolase 1, (alpha) Hs.254105 NM 001428 21471 at TDE1 tumor differentially expressed 1 Hs.272168 AW173623 6705 s at ADA adenosine deaminase Hs.1217 X02189 12415 at 37501 septin 6 Hs.90998 AW150913 15601 s at HOXB5 homeo box B5 Hs.22554 NM 002147 :09208 at MPDU1 mannose-P-dolichol utilization defect 1 Hs.6710 AF059752 methylenetetrahydrofolate dehydrogenase :02309_at MTHFD1 (NADP+ dependent), Hs.172665 NM 005956 methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase 01218_at CTBP2 C-terminal binding protein 2 Hs.171391 N23018 8188 s at TIMM13 translocase of inner mitochondrial Hs.23410 NM 012458 membrane 13 homolog (yeast) CD59 antigen p18-20 (antigen identified by 10983_x at CD59 monoclonal antibodies 16.3A5, EJ16, EJ30, Hs.278573 BF983379 EL32 and G344) )8964 s at FADS1 fatty acid desaturase 1 Hs.132898 AL512760 10365 at RUNX1 runt-related transcription factor 1 (acute Hs. 129914 D43967 - myeloid leukemia 1; amll oncogene) 0741 s at SID6-306 inorganic pyrophosphatase Hs.5123 NM006903 )3589 s at TFDP2 transcription factor Dp-2 (E2F dimerization Hs.19131 NM 006286 partner 2) 01664 at SMC4L1 SMC4 structural maintenance of Hs.50758 AL136877 -_chromosomes 4-like 1 (yeast) 8527 x at H2BFH H2B histone family, member H Hs.182138 NM_003523 01448_at TIA1 TIA1 cytotoxic granule-associated RNA Hs.239489 AL046419 - binding protein 5692_sat CD38 CD38 antigen (p45) Hs.66052 NM 001775 7727 x at VPS35 vacuolar protein sorting 35 (yeast) Hs.264190 NM 018206 17786 at SKB1 SKB1 homolog (S. pombe) Hs.12912 NM_006109 8585 s at RAMP RA-regulated nuclear matrix-associated Hs.126774 NM 016448 -_ -protein 15608 s at ANGPT1 angiopoietin 1 Hs.2463 U83508 05453 at HOXB2 homeo box B2 Hs.2733 NM 002145 14386 s at MRP63 mitochondrial ribosomal protein 63 Hs.182695 BF303597 0052 s at C20orfl chromosome 20 open reading frame 1 Hs.9329 AF098158 0911 1_at RNF5 ring finger protein 5 Hs.216354 BC004155 08898 at ATP6V1D ATPase, H+ transporting, lysosomal 34kD, Hs.272630 AF077614 - "IV subunit D 00821_at LAMP2 lysosomal-associated membrane protein 2 Hs.8262 NM_013995 40 WO 2006/125195 PCT/US2006/019614 Qualifier Gene Symbol Gene Name Unigene No. Accession No. 17719_x at KIAA0470 KIAA0470 gene product Hs.25132 NM 014812 MADS box transcription enhancer factor 2, )9199 s at MEF2C polypeptide C (myocyte enhancer factor Hs.78995 N22468 2C) 14500_at H2AFY H2A histone family, member Y Hs.75258 AF044286 09806 at H2B/S histone family member Hs.247817 BC000893 1028 s at MIC2 antigen identified by monoclonal antibodies Hs.177543 U82164 12E7, F21 and 013 6554 s_at ENO1 enolase 1, (alpha) Hs.254105 U88968 18099 at HT008 uncharacterized hypothalamus protein Hs.16206 NM_018469 -___ _ HT008 1581 s at WBSCR5 Williams-Beuren syndrome chromosome Hs.56607 AF257135 region 5 2294 s at Hs.165337 AW971415 03688_at PKD2 polycystic kidney disease 2 (autosomal Hs.82001 NM 000297 dominant) 00728 at ACTR2 ARP2 actin-related protein 2 homolog Hs.42915 BE566290 (yeast) 1562_sat SORD sorbitol dehydrogenase Hs.878 NM_003104 03608_at ALO31230 1714 x at FKBP1A FK506 binding protein 1A (12kD) Hs.179661 BC005838 7761 s._at DKFZP586A0522 DKFZP586A0522 protein Hs.288771 NM_014033 6057 x at SPN sialophorin (gpLIl15, leukosialin, CD43) Hs.80738 NM_003123 2739 s at NME4 non-metastatic cells 4, protein expressed in Hs.9235 AL523860 1060 x at EPB72 erythrocyte membrane protein band 7.2 Hs.160483 A537887 1060_-~at EPB72 (stomatin) Hs.160483 A1537887 0769_s at MAT2A methionine adenosyltransferase II, alpha Hs.77502 NM_005911 6445_sat HRMT1L2 HMT1 hnRNP methyltransferase-like 2 (S. Hs.20521 NM 001536 -___ cerevisiae) 8858 s at KIAA0747 KIAA0747 protein Hs.8309 BC004998 02546_at VAMP8 vesicle-associated membrane protein 8 Hs.172684 NM_003761 0_ at______ VM8(endobrevin) s.24 N 0 8279 s at H2AFO H2A histone family, member O Hs.795 BC001629 3253 s at KIAA0433 KIAA0433 protein Hs.26179 NM_015216 09177 at DKFZP564J0123 DKFZP564J0123 protein Hs.31387 BC002873 0549 s at SCYA23 small inducible cytokine subfamily A (Cys- Hs.169191 U58913 Cys), member 23 1329 s at ETS2 v-ets erythroblastosis virus E26 oncogene Hs.85146 NM_005239 homolog 2 (avian) 1301 s at ANXA4 annexin A4 Hs.77840 BC000182 01589_at SMC1L1 SMC1 structural maintenance of Hs.211602 D80000 chromosomes 1-like 1 (yeast) 4429 s at SLC2A5 solute carrier family 2 (facilitated Hs.33084 BE560461 Ss glucose/fructose transporter), member 5 0806_s_at HSPD1 heat shock 60kD protein 1 (chaperonin) Hs.79037 BE256479 12296_at POH1 26S proteasome-associated padl homolog Hs.178761 NM 005805 18160 at NDUFA8 NADH dehydrogenase (ubiquinone) 1 alpha Hs.31547 NM_014222 subcomplex, 8 (19kD, PGIV) )4039_at CEBPA CCAAT/enhancer binding protein (C/EBP), Hs.76171 NM 004364 alpha 0727 5sat ACTR2 ARP2 actin-related protein 2 homolog Hs.42915 AA699583 0_s_____ A_______TR2_______ (yeast) _ s.42915 AA699583 17814_at GK001 GK001 protein Hs.8207 NM 020198 41 WO 2006/125195 PCT/US2006/019614 ualifier Gene Symbol Gene Name Unigene No. Accession No. 2037 at MCM4 MCM4 minichromosome maintenance Hs.154443 A1859865 -________ ~deficient 4 (S. cerevisiae) s.5 3 A8 6 345 s at FABP5 fatty acid binding protein 5 (psoriasis- Hs.153179 NM_001444 - - associated) 040 s at HMBS hydroxymethylbilane synthase Hs.82609 NM 000190 071 xat TNRC1 1 trinucleotide repeat containing 11 (THR- Hs.211607 AF132033 07__a T associated protein, 230 kD subunit) 10812_at CCT7 chaperonin containing TCP1, subunit 7 (eta) Hs.108809 NM 006429 11098 at COPB2 coatomer protein complex, subunit beta 2 Hs.75724 NM 004766 (beta prime) 12974_at MPP1 membrane protein, palmitoylated 1 (55kD) Hs.1861 NM_002436 11577 at NME1 non-metastatic cells 1, protein (NM23A) Hs.118638 NM 000269 expressed in hypothetical protein FLJ22357 similar to 1686_sat FLJ22357 epidermal growth factor receptor-related Hs.57988 NM_022450 protein .8048_at BUP BUP protein Hs.35660 NM012071 11487 at CTSC cathepsin C Hs.10029 NM_001814 13196 at ABCC4 ATP-binding cassette, sub-family C Hs. 139336 AI948503 - (CFTR/MRP), member 4 )849_sat VPS41 vacuolar protein sorting 41 (yeast) Hs.180941 AF135593 1694 s at PCCB propionyl Coenzyme A carboxylase, beta Hs.63788 NM_000532 polypeptide 7799_x at UBE2H ubiquitin-conjugating enzyme E2H (UBC8 Hs.28505 NM 003344 homolog, yeast) )365 s at ECM1 extracellular matrix protein 1 Hs.81071 U65932 7988 at HEllO enhancerofinvasion 10 Hs.107003 NM 021178 kangai 1 (suppression of tumorigenicity 6, 1904 x at KAI prostate; CD82 antigen (R2 leukocyte Hs.323949 NM_002231 antigen, antigen detected by monoclonal and antibody IA4)) serine (or cysteine) proteinase inhibitor, )0986_at SERPINGI clade G (Cl inhibitor), member 1, Hs.151242 NM_000062 (angioedema, hereditary) )1491 at C14orf3 chromosome 14 open reading frame 3 Hs.204041 NM_012111 1663 s at SMC4L1 SMC4 structural maintenance of Hs.50758 NM 005496 chromosomes 4-like 1 (yeast) )942 s at HSBP1 heat shock factor binding protein 1 Hs.250899 NM_001537 )973 s at TSPAN-3 tetraspan 3 Hs.100090 NM 005724 7943_xat PLAGLI1 pleiomorphic adenoma gene-like 1 Hs.75825 NM_006718 3899 xat ATP6V1D ATPase, H+ transporting, lysosomal 34kD, Hs.272630 AF100741 VI subunit D )240 s at FLJ20623 hypothetical protein FLJ20623 Hs.27337 NM_017905 [8966_at MYO5C myosin 5C Hs.111782 NM_018728 )026 xat FKBPI1A FK506 binding protein lA (12kD) Hs.179661 AF141349 1403 sat MGST3 microsomal glutathione S-transferase 3 Hs.111811 NM_004528 3113 s at DKFZp762A227 hypothetical protein DKFZp762A227 Hs.274453 AI630178 3971 sat JJAZ1 joined to JAZFI Hs.197803 AI924660 1769_x at TDE1 tumor differentially expressed 1 Hs.272168 BC006088 1161 s at CSDA cold shock domain protein A Hs.198726 NM 003651 )2990_at PYGL phosphorylase, glycogen; liver (Hers Hs.771 NM_002863 -__ disease, glycogen storage disease type VI) 3418 sat DKFZP434N161 DKFZP434N161 protein Hs.284208 NM_015493 42 WO 2006/125195 PCT/US2006/019614 Jalifier Gene Symbol Gene Name Unigene No. Accession No. protein phosphatase 3 (formerly 2B), 429 s at PPP3CA catalytic subunit, alpha isoform (calcineurin Hs.272458 AL353950 A alpha) 9215 at TETRAN tetracycline transporter-like protein Hs.157145 Ll 1669 949_s_at IMAGE3455200 hypothetical protein IMAGE3455200 Hs.324844 NM 024006 499_sat CHC1 chromosome condensation 1 Hs.84746 NM001269 8027 at MRPL15 mitochondrial ribosomal protein L15 Hs.18349 NM014175 9479 aMGC5302 endoplasmic reticulum resident protein 58; Hs.44970 NM_024089 7at MGC5302 hypothetical protein MGCS302 s.47 N 028 880 s at C20orfl4 chromosome 20 open reading frame 14 Hs.31334 AB019219 416 s at STOML2 stomatin (EPB72)-like 2 Hs.3439 AC004472 9559 at C20orf59 chromosome 20 open reading frame 59 Hs.353013 NM 022082 342 x at TNRC1 1 trinucleotide repeat containing 11 (THR- Hs.211607 BC004354 32x aTassociated protein, 230 kD subunit) s.10B 03 7724_at PAI-RBP1 PAI-1 mRNA-binding protein Hs.165998 AF131807 2330_at TFDP1 transcription factor Dp-1 Hs.79353 R60866 8817 at COMT catechol-O-methyltransferase Hs.240013 BC000419 4040 at KIAA0161 KIAA0161 gene product Hs.78894 NM 014746 3854 at SYNGR1 synaptogyrin 1 Hs.6139 BF511590 1729 s at ACTR2 ARP2 actin-related protein 2 homolog Hs.42915 NM005722 (yeast) 1970 s at NASP nuclear autoantigenic sperm protein Hs.243886 NM_002482 (histone-binding) 13021 at SLPI secretory leukocyte protease inhibitor Hs.251754 NM 003064 __- (antileukoproteinase) FFX-r2 I8SrRNA- M11167 3 at )900 s at M6PR mannose-6-phosphate receptor (cation Hs.75709 AI583537 dependent) 1800 sat MRPS14 mitochondrial ribosomal protein S14 Hs.247324 BG254653 12320_at BC001002 7892 s at ARL4, EPLIN ADP-ribosylation factor-like 4, epithelial Hs.10706 NM_016357 2_sat_ A Pprotein lost in neoplasm beta 18270_at MRPL24 mitochondrial ribosomal protein L24 Hs.9265 NM_024540 )2567 at SNRPD3 small nuclear ribonucleoprotein D3 Hs.1575 NM_004175 2_ at___ SNRPD3polypeptide (18kD) _ )1302 at ANXA4 annexin A4 Hs.77840 NM_001153 4113_s at RBM8A RNA binding motif protein 8A Hs.10283 AI738479 5438_x at FLJ12975 hypothetical protein FLJ12975 Hs.167165 NM_024809 0683_sat UBE2L3 ubiquitin-conjugating enzyme E2L 3 Hs. 108104 BE964689 glucosaminyl (N-acetyl) transferase 1, core )5505_at GCNT1 2 (beta-1,6-N- Hs.159642 NM_001490 acetylglucosaminyltransferase) 8055_s _at FLJ10904 hypothetical protein FLJ10904 Hs.16470 NM_018268 9515 sat RAB27A RAB27A, member RAS oncogene family Hs.50477 U38654 21831 at Hs.348898 AV741657 1942_s at GUCY1A3 guanylate cyclase 1, soluble, alpha 3 Hs.75295 AI719730 13797_at cig5 vipirin Hs.17518 AI337069 9517_s at ASH2L ash2 (absent, small, or homeotic)-like Hs.6 856 AB020982 9_sat__ ASH2L _ ~(Drosophila) s.8029 43 WO 2006/125195 PCT/US2006/019614 Qualifier Gene Symbol Gene Name Unigene No. Accession No. 3330 s at STIP1 stress-induced-phosphoprotein 1 Hs.75612 BE886580 sat STIPI (Hsp70/Hsp90-organizing protein) 3617_s at DKFZP586M1523 DKFZP586M1523 protein Hs.22981 BF063896 tumor necrosis factor receptor superfamily, 9423_xat TNFRSF12 member 12 (translocating chain-association Hs.180338 NM_003790 membrane protein) 5626 at SGSH N-sulfoglucosamine sulfohydrolase Hs.31074 U30894 - (sulfamidase) 7314 x at KIR3DL2 killer cell immunoglobulin-like receptor, Hs.56328 NM 006737 three domains, long cytoplasmic tail, 2 11984 at Hs.374441 AI653730 03848 at AKAP8 A kinase (PRKA) anchor protein 8 Hs.25059 AL050160 0965 sat ABLIM actin binding LIM protein Hs.158203 NM 006720 01531 at ZFP36 zinc finger protein 36, C3H type, homolog Hs.343586 NM 003407 (mouse) 7509_sat LAIR2 leukocyte-associated Ig-like receptor 2 Hs.43803 NM_002288 5022_sat CHESI1 checkpoint suppressor 1 Hs.211773 NM_005197 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), 7697_xat LILRB1, LILRB2 member 1, leukocyte immunoglobulin-like Hs.22405 NM_005874 receptor, subfamily B (with TM and ITIM domains), member 2 5019 s at VIPR1 vasoactive intestinal peptide receptor 1 Hs.348500 NM_004624 0845_s at PLAUR plasminogen activator, urokinase receptor Hs.179657 U08839 03341 at CBF2 CCAAT-box-binding transcription factor Hs.184760 NM_005760 9657_sat HSF2 heat shock transcription factor 2 Hs.158195 M65217 20684 at TBX21 T-box21 Hs.272409 NM 013351 03118 at PCSK7 proprotein convertase subtilisin/kexin type Hs.32978 NM_004716 7 1924 s at PLAUR plasminogen activator, urokinase receptor Hs. 179657 AY029180 DiGeorge syndrome critical region gene 12032 at DGSI DGSI; likely ortholog of mouse expressed Hs.154879 L77566 sequence 2 embryonic lethal 8878 s at SIRTI sirtuin silent mating type information Hs.31176 NM 012238 regulation 2 homolog 1 (S. cerevisiae) 12914_at PKP4 plakophilin 4 Hs.152151 AV648364 04847_at ZNF-U69274 zinc finger protein Hs.301956 NM_014415 06110_at H3FK H3 histone family, member K Hs.70937 NM_003536 3587 s_at Hs.351612 AI884867 03547at CD4 CD4 antigen (p55) Hs.17483 U47924 14696 at MGC14376 hypothetical protein MGC14376 Hs.29206 AF070569 20088 at C5R1 complement component 5 receptor 1 (C5a Hs.2161 NM 001736 -________ _ligand) 2724_s at FOXO1A forkhead box O1A (rhabdomyosarcoma) Hs.170133 NM_002015 0788_s at PEA15 phosphoprotein enriched in astrocytes 15 Hs.194673 NM_003768 1393_s at IGF2R insulin-like growth factor 2 receptor Hs.76473 NM_000876 13376at Hs.372699 AI656706 4621 s at NR4A2 nuclear receptor subfamily 4, group A, Hs.82120 AI935096 4_ sat RAmember 2 14945 at KIAA0752 KIAA0752 protein Hs.126779 AW514267 21757 at MGC17330 hypothetical protein MGC17330 Hs.26670 BE042976 44 WO 2006/125195 PCT/US2006/019614 ualifier Gene Symbol Gene Name Unigene No. Accession No. 985 sat Hs.374441 AI653730 '871 s at PSAP prosaposin (variant Gaucher disease and Hs.78575 NM 002778 variant metachromatic leukodystrophy) 842 s at DNAJB9 DnaJ (Hsp40) homolog, subfamily B, Hs.6790 AL080081 member 9 9155_at RDGBB retinal degeneration B beta Hs.333212 NM 012417 '3234_at UP uridine phosphorylase Hs.77573 NM 003364 .170 sat BHLHB2 basic helix-loop-helix domain containing, Hs.171825 NM 003670 170_sa BHLH2 class B, 2 973 sat CEBPD CCAAT/enhancer binding protein (C/EBP), Hs.76722 NM 005195 sat CEBPD delta 9040_at FLJ22021 hypothetical protein FLJ22021 Hs.7258 NM 024535 4714 at FLJ12298 hypothetical protein FLJ12298 Hs.284168 AK022360 9279_at FLJ20220 hypothetical protein FLJ20220 Hs.21126 NM017718 0420 at STKO10 serine/threonine kinase 10 Hs.16134 AB015718 4467_at GPR65 G protein-coupled receptor 65 Hs.131924 NM 003608 )2518_at BCL7B B-cell CLL/lymphoma 7B Hs.16269 NM001707 1224 s at GCH1 GTP cyclohydrolase 1 (dopa-responsive Hs.86724 NM 000161 dystonia) )3045 at NINJI ninjurin 1 Hs.11342 NM 004148 9582 at Hs.26295 AL050166 leukocyte immunoglobulin-like receptor, )225_xat LILRB3 subfamily B (with TM and ITIM domains), Hs.105928 AF009635 member 3 1891 sat LCK lymphocyte-specific protein tyrosine kinase Hs.1765 NM 005356 3711 s at SDPR serum deprivation response Hs.26530 NM_004657 1 sat SDPR (phosphatidylserine binding protein) t615 x_at IDI1 isopentenyl-diphosphate delta isomerase Hs.76038 NM 004508 )9959 at NR4A3 nuclear receptor subfamily 4, group A, Hs.80561 U12767 at NR4A3 member 3 5254 xat TCF7 transcription factor 7 (T-cell specific, Hs.169294 AW027359 HMG-box) 1396 s _at GPRKS G protein-coupled receptor kinase 5 Hs.211569 NM 005308 18319 at PELI1 pellino homolog 1 (Drosophila) Hs.7886 NM 020651 )4369 at PIK3CA phosphoinositide-3-kinase, catalytic, alpha Hs.85701 NM 006218 4__ _ PK3Apolypeptide 1662 s at FACL3 fatty-acid-Coenzyme A ligase, long-chain 3 Hs.268012 D89053 2998 x at HLA-DQBI major histocompatibility complex, class II, Hs.73931 AI583173 DQ beta 1 0921 s at BTG1 B-cell translocation gene 1, anti- Hs.77054 NM 001731 proliferative 4588 s at SLC7A7 solute carrier family 7 (cationic amino acid Hs.194693 NM_003982 transporter, y+ system), member 7 8881 xat IDI1 isopentenyl-diphosphate delta isomerase Hs.76038 BC005247 02861 at PERI period homolog 1 (Drosophila) Hs.68398 NM 002616 2464_s at PFKFB3 6-phosphofructo-2-kinase/fructose-2,6- Hs.195471 NM 004566 biphosphatase 3 02388_at RGS2 regulator of G-protein signalling 2, 24kD Hs.78944 NM 002923 19118_at FKBP 11 FK506 binding protein 11 (19 kDa) Hs.24048 NM_016594 13906 at MYBL1 v-myb myeloblastosis viral oncogene Hs.300592 AW592266 - homolog (avian)-like 1 2880 s at PSCD1 pleckstrin homology, Sec7 and coiled/coil Hs.1050 NM_004762 -8_______ - ____ ____ domains 1(cytohesin 1) Hs.1050 NM004762 45 WO 2006/125195 PCT/US2006/019614 qualifier Gene Symbol Gene Name Unigene No. Accession No. L631 s at IER3 immediate early response 3 Hs.76095 NM_003897 3758 at Hs.373513 AW337510 )616 s at CES1 carboxylesterase 1 (monocyte/macrophage Hs.76688 S73751 -___ _ -serine esterase 1) 5281 s at PIGA phosphatidylinositol glycan, class A Hs.51 NM_002641 (paroxysmal nocturnal hemoglobinuria) )4215 at MGC4175 hypothetical protein MGC4175 Hs.322404 NM_024315 )2478_at GS3955 GS3955 protein Hs.155418 NM_021643 [2812 at Hs.288232 AI700633 7826 s at ID3 inhibitor of DNA binding 3, dominant Hs.76884 NM 002167 negative helix-loop-helix protein 18764 at MGC5363 hypothetical protein MGC5363 Hs.1880 NM_024064 )2072 at HNRPL heterogeneous nuclear ribonucleoprotein L Hs.2730 NM_001533 [10439_at ICOS inducible T-cell co-stimulator Hs.56247 AB023135 )3320 at LNK lymphocyte adaptor protein Hs.13131 NM_005475 )4440 at CD83 CD83 antigen (activated B lymphocytes, Hs.79197 NM 004233 -_________ immunoglobulin superfamily) H.97M043 1458 s at GABARAPL3 GABA(A) receptors associated protein like Hs.334497 AF180519 -- -- 3 12769 at TLE3 transducin-like enhancer of split 3 (E(spl) Hs.287362 AI567426 i276 at3homolog, Drosophila) 1841 s at KLF4 Kruppel-like factor 4 (gut) Hs.356370 BF514079 17784_at YKT6 SNARE protein Ykt6 Hs.296244 BE384482 2782 s at SKIP skeletal muscle and kidney enriched inositol Hs.178347 NM 016532 phosphatase 0987 s at DKFZP434JO37 hypothetical protein DKFZp434JO37 Hs.172012 NM 030952 18708 at NXT1 NTF2-like export factor 1 Hs.24563 NM 013248 5785 s at CYFIP2 cytoplasmic FMR1 interacting protein 2 Hs.258503 AL161999 32969_at Hs.372643 AI216690 protein phosphatase 3 (formerly 2B), 7000 s at PPP3CC catalytic subunit, gamma isoform Hs.75206 NM_005605 (calcineurin A gamma) 3146 sat GABBR1 gamma-aminobutyric acid (GABA) B Hs.167017 NM 001470 146sat GABBR1 receptor, 1 33555 at PTPN18 protein tyrosine phosphatase, non-receptor Hs.278597 NM 014369 type 18 (brain-derived) 6130 s at ASGR2 asialoglycoprotein receptor 2 Hs. 1259 NM_001181 2928 sat PHF1 PHD finger protein 1 Hs.166204 NM_024165 4627 s at ITGB3 integrin, beta 3 (platelet glycoprotein IIIa, Hs.87149 M35999 antigen CD61) 09674 at CRY1 cryptochrome 1 (photolyase-like) Hs.151573 D83702 0319 s at MIR myosin regulatory light chain interacting Hs.20072 NM 013262 protein T-cell, immune regulator 1, ATPase, H+ 4158_sat TCIRG1 transporting, lysosomal V0 protein a Hs.46465 NM_006019 isoform 3 04731 at TGFBR3 transforming growth factor, beta receptor III Hs.342874 NM 003243 _at TGFBR3 (betaglycan, 300kD) 22315_at Hs.292853 AW972855 14617 at PRF1 perforin 1 (pore forming protein) Hs.2200 AI445650 2284 s at CDKNIA cyclin-dependent kinase inhibitor 1A (p 2 1 , Hs.179665 NM_000389 2284_____a __ DKN_1A _ Cip1) l)_796 1429 s at SERPINA1 serine (or cysteine) proteinase inhibitor, Hs.297681 AF119873 46 WO 2006/125195 PCT/US2006/019614 lalifier Gene Symbol Gene Name Unigene No. Accession No. clade A (alpha- 1 antiproteinase, antitrypsin), member 1 ?19 s at CXCR4 chemokine (C-X-C motif), receptor 4 Hs.89414 AF348491 (fusin) Z508 at MAP-1 modulator of apoptosis 1 Hs.24719 AK024029 472 s at TLE3 transducin-like enhancer of split 3 (E(spl) Hs.287362 NM 005078 7____ aLhomolog, Drosophila) 761 s at SYNE-2 synaptic nuclei expressed gene 2 Hs.57749 NM_015180 leukocyte immunoglobulin-like receptor, 146_x_at LILRB2 subfamily B (with TM and ITIM domains), Hs.22405 AF004231 member 2 193_x at TRB@ T cell receptor beta locus Hs.303157 AL559122 5275_at AW963138 5070_at ING3 inhibitor of growth family, member 3 Hs.143198 NM_019071 890 s at LOC51202 hqp0256 protein Hs.284288 NM_016355 606 x at KLRD1 killer cell lectin-like receptor subfamily D, Hs.41682 U30610 member 1 phosphodiesterase 4D, cAMP-specific 4491 at PDE4D (phosphodiesterase E3 dunce homolog, Hs.172081 R40917 Drosophila) 0066 at CARD15 caspase recruitment domain family, Hs.135201 NM 022162 - member 15 8964 at DRIL2 dead ringer (Drosophila)-like 2 (bright and Hs.10431 NM006465 dead ringer) .019 s at DKFZP586Fl318 hypothetical protein DKFZP586Fl318 Hs.25213 NM 015677 688_sat MGC13033 hypothetical protein MGC13033 Hs.26118 BC005078 2400 at Hs.349755 AL043266 8032 at SNN stannin Hs.76691 AF070673 16337 at CCR7 chemokine (C-C motif) receptor 7 Hs.1652 NM 001838 C-type (calcium dependent, carbohydrate 9947_at CLECSF6 recognition domain) lectin, superfamily Hs.115515 NM_016184 member 6 )4912_at IL10RA interleukin 10 receptor, alpha Hs.327 NM_001558 )7840 at BY55 natural killer cell receptor, immunoglobulin Hs.81743 NM 007053 superfamily member )495 _at ARHH ras homolog gene family, member H Hs.109918 NM_004310 t049 x at CD7 CD7 antigen (p41) Hs.36972 AI829961 3831 s at FCGRT Fc fragment of IgG, receptor, transporter, Hs. 11903 NM 004107 -_ _ -alpha )8450 at LGALS2 lectin, galactoside-binding, soluble, 2 Hs.113987 NM006498 (galectin 2) _ 5992 sat IL15 interleukin 15 Hs.168132 NM 000585 )6118 at STAT4 signal transducer and activator of Hs.80642 NM 003151 transcription 4 8309 sat MALT1 mucosa associated lymphoid tissue Hs.180566 NM 006785 9sat MALT1 lymphoma translocation gene ;0084_at CYLD cylindromatosis (turban tumor syndrome) Hs.18827 AI453099 2693_sat STKl7A serine/threonine kinase 17a (apoptosis- Hs.9075 AW194730 inducing) D7460_at GZMM granzyme M (lymphocyte met-ase 1) Hs.268531 NM_005317 4487 s at KCNQ1 potassium voltage-gated channel, KQT-like Hs.156115 NM 000218 subfamily, member 1 7838 sat RNB6 RNB6 Hs.241471 NM_016337 2833 sat SERPINA1 serine (or cysteine) proteinase inhibitor, Hs.297681 NM_000295 47 WO 2006/125195 PCT/US2006/019614 qualifier Gene Symbol Gene Name Unigene No. Accession No. clade A (alpha-1 antiproteinase, antitrypsin), member 1 )915 x at TRB@ T cell receptor beta locus Hs.303157 M15564 HLA-DQA1, HLA- major histocompatibility complex, class II, D671 s at DQ alpha 1, major histocompatibility Hs.198253 BG397856 DQA2 complex, class II, DQ alpha 2 7339 s at LTB lymphotoxin beta (TNF superfamily, Hs.890 NM_002341 sat LTB member 3) C-type (calcium dependent, carbohydrate 1724 s at CLECSF6 recognition domain) lectin, superfamily Hs. 115515 AF200738 member 6 1059 s at CHST6 carbohydrate (N-acetylglucosamine 6-0) Hs.157439 NM 021615 1059satHST sulfotransferase 6 )201 x at CXCR4 chemokine (C-X-C motif), receptor 4 Hs.89414 L01639 - -(fusin) 12501 at CEBPB CCAAT/enhancer binding protein (C/EBP), Hs.99029 AL564683 beta )1739 at SGK serum/glucocorticoid regulated kinase Hs.296323 NM_005627 )7072 at IL18RAP interleukin 18 receptor accessory protein Hs.158315 NM_003853 0920 sat BTG1 B-cell translocation gene 1, anti- Hs.77054 AL535380 9 _a proliferative )3334 at DDX8 DEAD/H (Asp-Glu-Ala-Asp/His) box Hs.171872 NM 004941 at DDX8 polypeptide 8 (RNA helicase) 4622 x at NR4A2 nuclear receptor subfamily 4, group A, Hs.82120 NM_006186 member 2 12231 at FBXO21 F-box only protein 21 Hs.184227 AB020682 2968 s at DYRK2 dual-specificity tyrosine-(Y)- Hs.173135 Y09216 phosphorylation regulated kinase 2 2637 s at ICAMI intercellular adhesion molecule 1 (CD54), Hs.168383 A1608725 human rhinovirus receptor 13539 at CD3D CD3D antigen, delta polypeptide (TiT3 Hs.95327 NM 000732 complex) 05291_at IL2RB interleukin 2 receptor, beta Hs.75596 NM_000878 2723 s at FOXO1A forkhead box 01A (rhabdomyosarcoma) Hs.170133 AW117498 6343 s at NRG1 neuregulin 1 Hs.172816 NM_013959 3543 sat BTEB1 basic transcription element binding protein Hs.150557 NM_001206 3s.1_at BTEB1 I 2644 s at TNFAIP3 tumor necrosis factor, alpha-induced protein Hs.211600 NM 006290 3 9345 s at PI4KII phosphatidylinositol 4-kinase type II Hs.25300 AL561930 19622 at RAB20 RAB20, member RAS oncogene family Hs.179791 NM 017817 9528 s at BCL11B B-cell CLL/lymphoma 1 B (zinc finger Hs.57987 NM_022898 -_ -protein) 17591 at Hs.272108 BF725121 1796 s at TRB@ T cell receptor beta locus Hs.303157 AF043179 4838 s at MLH3 mutL homolog 3 (E. coli) Hs.279843 NM_014381 13915 at NKG7 natural killer cell group 7 sequence Hs.10306 NM_005601 6248 s at NR4A2 nuclear receptor subfamily 4, group A, Hs.82120 S77154 6248saR4A ~member 2 3142 x at LOC54103 hypothetical protein Hs.12969 AV700415 03888_at THBD thrombomodulin Hs.2030 NM 000361 tumor necrosis factor receptor superfamily, 1841_s at TNFRSFI2 member 12 (translocating chain-association Hs.180338 U94510 membrane protein) N 001 04118_at CD48 CD48 antigen (B-cell membrane protein) Hs.901 NM_001778 48 WO 2006/125195 PCT/US2006/019614 qualifier Gene Symbol Gene Name Unigene No. Accession No. 2841 s at PPFIBP2 PTPRF interacting protein, binding protein Hs.12953 AI692180 2 (liprin beta 2) 5255 x at TCF7 transcription factor 7 (T-cell specific, Hs.169294 NM 003202 HMG-box) 9871 s at APBA2 amyloid beta (A4) precursor protein- Hs.26468 AB014719 -_ -binding, family A, member 2 (X 1 -like) 3601 s at TUBB1 tubulin, beta 1 Hs.303023 NM_030773 18454 at FLJ22662 hypothetical protein FLJ22662 Hs.178470 NM_024829 9536 s at EHD4 EH-domain containing 4 Hs.356052 AF320070 phosphodiesterase 4B, cAMP-specific )3708_at PDE4B (phosphodiesterase E4 dunce homolog, Hs.188 NM 002600 Drosophila) 2048 s at CBX6 chromobox homolog 6 Hs.107374 NM_014292 8078 s at TCF8 transcription factor 8 (represses interleukin Hs.232068 NM 030751 2 expression) 39447 at SYNE-1 synaptic nuclei expressed gene lb Hs.8182 AF043290 12313 at Hs.5019 BC004344 8205 s at MKNK2 MAP kinase-interacting serine/threonine Hs.372455 NM 017572 kinase 2 9824 s at ARNTL aryl hydrocarbon receptor nuclear Hs.74515 AB000812 translocator-like 13958 at CD6 CD6 antigen Hs.81226 AW134823 1558 s at LEF1 lymphoid enhancer-binding factor 1 Hs.44865 AF288571 7911 sat BAG3 BCL2-associated athanogene 3 Hs.15259 NM_004281 8622 s at VIL2 villin 2 (ezrin) Hs.155191 AA670344 18345 at HCA112 hepatocellular carcinoma-associated antigen Hs.12126 NM 018487 112 4777_s at MAL mal, T-cell differentiation protein Hs.80395 NM_002371 13300 at KIAAO404 KIAAO404 protein Hs.105850 AW168132 10054_at MGC4701 hypothetical protein MGC4701 Hs.116771 BC003648 9117 s at FKBP11 FK506 binding protein 11 (19 kDa) Hs.24048 NM_016594 4244 s at ASK activator of S phase kinase Hs.152759 NM 006716 02531 at IRFI interferon regulatory factor 1 Hs.80645 NM_002198 22142 at CYLD cylindromatosis (turban tumor syndrome) Hs.18827 AK024212 05241 at SCO2 SCO cytochrome oxidase deficient homolog Hs.278431 NM 005138 2 (yeast) 02320 at GTF3CI general transcription factor IIIC, Hs.331 NM 001520 23_ polypeptide 1 (alpha subunit, 220kD) 04103 at SCYA4 small inducible cytokine A4 Hs.75703 NM_002984 leukocyte immunoglobulin-like receptor, 6881 s at LILRA3 subfamily A (without TM domain), member Hs. 113277 NM_006865 3 12956_at KIAA0882 KIAA0882 protein Hs.90419 AI348094 1583 x at LY117 lymphocyte antigen 117 Hs.88411 AF031136 1962 s at ZFP36L1 zinc finger protein 36, C3H type-like 1 Hs.85155 BG250310 04411 at KIAA0449 KIAA0449 protein Hs.169182 NM 017596 8657 s at MSF MLL septin-like fusion Hs.181002 AF142408 19593 at PHT2 peptide transporter 3 Hs.237856 NM 016582 2150 s at LOC54103 hypothetical protein Hs.12969 AK026747 01425 at ALDH2 aldehyde dehydrogenase 2 family Hs.195432 NM_000690 - (mitochondrial) 49 WO 2006/125195 PCT/US2006/019614 ?ualifier Gene Symbol Gene Name Unigene No. Accession No. 11565 s at ID2 inhibitor of DNA binding 2, dominant Hs.180919 NM 002166 15_s_ aID2negative helix-loop-helix protein 12643 s at TNFAIP3 tumor necrosis factor, alpha-induced protein Hs.211600 A1738896 09501 at CDR2 cerebellar degeneration-related protein Hs.75124 AL582414 -_ (62kD) 21890 at ZNF335 zinc finger protein 335 Hs.165983 NM_022095 '2295 sat CTSH cathepsin H Hs.288181 NM 004390 01341 at ENCI ectodermal-neural cortex (with BTB-like Hs.104925 NM 003633 -__________ domain) s.095 N 036 phosphodiesterase 4D, cAMP-specific 1840 s at PDE4D (phosphodiesterase E3 dunce homolog, Hs.172081 U50157 Drosophila) 18486 at TIEG2 TGFB inducible early growth response 2 Hs.12229 AA149594 12196_at Hs.71968 AW242916 19359_at FLJ22635 hypothetical protein FLJ22635 Hs.288529 NM 025092 04655 at SCYA5 small inducible cytokine A5 (RANTES) Hs.241392 NM 002985 small inducible cytokirne subfamily C, 6366_xat SCYC1, SCYC2 member 1 (lymphotactin), small inducible Hs.3195 U23772 cytokine subfamily C, member 2 pro-platelet basic protein (includes platelet 4146 s at PPBP basic protein, beta-thromboglobulin, Hs.2164 R64130 - - connective tissue-activating peptide III, neutrophil-activating peptide-2) 18037_at DTR diphtheria toxin receptor (heparin-binding Hs.799 M60278 epidermal growth factor-like growth factor) 9062 xat NCOA3 nuclear receptor coactivator 3 Hs.225977 AF010227 3524 s at GOS2 putative lymphocyte GO/G1 switch gene Hs.95910 NM 015714 13135 at Hs.82141 U90902 2524 s at KIAAO275 KIAAO275 gene product Hs.74583 NM 014767 0479 s at RORA RAR-related orphan receptor A Hs.2156 L14611 10279 at GPR18 G protein-coupled receptor 18 Hs.88269 AF261135 405 i at SCYA5 small inducible cytokine A5 (RANTES) Hs.241392 M21121 4198 sat RUNX3 runt-related transcription factor 3 Hs.170019 AA541630 1566_xat ID2 inhibitor of DNA binding 2, dominant Hs.180919 D13891 negative helix-loop-helix protein 4197_s at RUNX3 runt-related transcription factor 3 Hs.170019 NM 004350 8793 sat SCMLI1 sex comb on midleg-like 1 (Drosophila) Hs. 109655 NM 006746 09728_at HLA-DRB4 major histocompatibility complex, class II, Hs.318720 BC005312 DR beta 4 02206_at ARL7 ADP-ribosylation factor-like 7 Hs.111554 AW450363 13624 at ASM3A acid sphingomyelinase-like Hs.42945 AA873600 - phosphodiesterase 18696 at EIF2AK3 eukaryotic translation initiation factor 2- Hs.102506 NM 004836 _ alpha kinase 3 12195_at Hs.71968 AL049265 5296 xat MAP4K1 mitogen-activated protein kinase kinase Hs.86575 NM 007181 - -kinase kinase 1 1189 sat ITPR3 inositol 1,4,5-triphosphate receptor, type 3 Hs.77515 NM 002224 19099_at C12orf5 chromosome 12 open reading frame 5 Hs.24792 NM 020375 Z187. xat PTGDS prostaglandin D2 synthase (2 lkD, brain) Hs.8272 NM 000954 9604_s._at GATA3 GATA binding protein 3 Hs. 169946 BC003070 50 WO 2006/125195 PCT/US2006/019614 qualifier Gene Symbol Gene Name Unigene No. Accession No. )4794 at DUSP2 dual specificity phosphatase 2 Hs.1183 NM_004418 )113 s_at DEFCAP death effector filament-forming Ced-4-like Hs.104305 AF310105 apoptosis protein )4790 at MADH7 MAD, mothers against decapentaplegic Hs.100602 NM 005904 a Dhomolog 7 (Drosophila) 2208 s at ARL7 ADP-ribosylation factor-like 7 Hs.111554 BC001051 )3821 at DTR diphtheria toxin receptor (heparin-binding Hs.799 NM 001945 epidermal growth factor-like growth factor) small inducible cytokine subfamily C, 567 s at SCYCI, SCYC2 member 1 (lymphotactin), small inducible Hs.174228 NM_003175 cytokine subfamily C, member 2 3887 sat THBD thrombomodulin Hs.2030 NM 000361 5655 s at GP1BB glycoprotein Ib (platelet), beta polypeptide Hs.283743 NM_000407 1219 x at MAP4K1 mitogen-activated protein kinase kinase Hs.86575 BE646618 2_ at_ MAP4K _ kinase kinase 1 )4793 at KIAA0443 KIAA0443 gene product Hs.113082 NM 014710 14470 at KLRB1 killer cell lectin-like receptor subfamily B, Hs. 169824 NM_002258 Member 1I )2207 at ARL7 ADP-ribosylation factor-like 7 Hs.111554 BG435404 2988 s at RGS 1 regulator of G-protein signalling 1 Hs.75256 NM 002922 1748 x at PTGDS prostaglandin D2 synthase (21kD, brain) Hs.8272 BC005939 10164 at GZMB granzyme B (granzyme 2, cytotoxic T- Hs. 1051 J03189 - lymphocyte-associated serine esterase 1) 21756 at MGC17330 hypothetical protein MGC17330 Hs.26670 AL540260 8146 s at CPVL carboxypeptidase, vitellogenic-like Hs.95594 NM_031311 5390 x at PF4 platelet factor 4 Hs.81564 NM_002619 14032 at ZAP70 zeta-chain (TCR) associated protein kinase Hs.234569 AI817942 - (70 kD) 16834 at RGS1 regulator of G-protein signalling I Hs.75256 559049 0426 x at RORA RAR-related orphan receptor A Hs.2156 U04897 0646 s at KLRF1 killer cell lectin-like receptor subfamily F, Hs.183125 NM_016523 member 1 03414 at MMD monocyte to macrophage differentiation- Hs.79889 NM 012329 - associated 0512 s at VEGF vascular endothelial growth factor Hs.73793 AF022375 3271 s at UNC119 unc-119 homolog (C. elegans) Hs.81728 NM_005148 04081 at NRGN neurogranin (protein kinase C substrate, Hs.26944 NM_006176 - RC3) 04115 at GNG11 guanine nucleotide binding protein 11 Hs.83381 NM_004126 17145 at GNLY granulysin Hs.105806 M85276 5495 s at GNLY granulysin Hs.105806 NM 006433 05237 at FCN1 ficolin (collagen/fibrinogen domain Hs.252136 NM 002003 - containing) 1 10031 at CD3Z CD3Z antigen, zeta polypeptide (TiT3 Hs.97087 J04132 - complex) 0532 sat LR8 LR8 protein Hs.190161 NM 014020 1211 s at C21orf7 chromosome 21 open reading frame 7 Hs.41267 NM_020152 01506 at TGFBI transforming growth factor, beta-induced, Hs.118787 NM 000358 -_ 68kD 51 WO 2006/125195 PCT/US2006/019614 [0045] Each qualifier on a HG-U133A Genechip@ represents a set of oligonucleotide probes (PM or perfect match probe) that are stably attached to the respective regions on the Genechip®. The RNA transcript (or the complement thereof) of the gene identified by a qualifier can hybridize under nucleic acid array hybridization conditions to at least one oligonucleotide probe of the qualifier. Preferably, the RNA transcript (or the complement thereof) of the gene does not hybridize under nucleic acid array hybridization conditions to the mismatch (MM) probes of the qualifier. A mismatch probe is identical to the corresponding PM probe except for a single, homomeric substitution at or near the center of the mismatch probe. For instance, the MM probe for a 25-mer PM probe has a homomeric base change at the 13th position. [0046] In one embodiment, the RNA transcript (or the complement thereof) of the gene identified by a qualifier can hybridize under nucleic acid array hybridization conditions to at least 50%, 60%, 70%, 80%, 90% or 100% of the PM probes of the qualifier, but not to the corresponding mismatch probes. The discrimination score (R) for each of these PM probes, as measured by the ratio of the hybridization intensity difference of the corresponding probe pair (i.e., PM - MM) over the overall hybridization intensity (i.e., PM + MM), can be no less than 0.015, 0.02, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5 or greater. In another embodiment, the RNA transcript (or the complement thereof) of the gene, when hybridized to a HG-U133A Genechip® according to the manufacturer's instructions, produces a "present" call at the corresponding qualifier under the default settings (i.e., the threshold Tau is 0.015 and the significance level a, is 0.4). See Genechip® Expression Analysis Data Analysis Fundamentals (Part No. 701190 Rev. 2, Affymetrix, Inc., 2002), the entire content of which is incorporated herein by reference. [0047] The sequences of each PM probe on HG-U133A Genechips®, and the target sequences from which the PM probes are derived, can be readily obtained from Affymetrix's sequence database at Affymetrix website. See, for example, HG Ul133A_probe tab.zip, the entire content of which is incorporated herein by reference. 52 WO 2006/125195 PCT/US2006/019614 [0048] Table 2 lists the genes that are represented by the qualifiers in Table 1. These genes, as well as their corresponding unigene IDs and Entrez accession numbers, were identified according to Affymetrix Genechip® annotation. A unigene is composed of a non-redundant set of gene-oriented clusters. Each unigene cluster is believed to include sequences that represent a unique gene. The Entrez database collects sequences from a variety of sources, such as GenBank, RefSeq and PDB. The oligonucleotide probes of each qualifier can be derived from its corresponding Entrez sequence. [00491 Table 3 describes qualifiers that showed elevated or decreased signals when hybridized to MDS samples as compared to disease-free samples. The average hybridization signals at each qualifier for MDS ("MDS Average") or disease-free ("Disease-Free Average") samples are provided, together with their corresponding standard deviations ("MDS StDev" and "Disease-Free StDev," respectively). In addition, the ratios between the average hybridization signals ("MDS/Disease-Free") and the p-values of Student's test (two-tailed distribution, two-sample unequal variance) for the observed differences are also provided. Table 4 further describes the genes that are represented by the qualifier in Table 3. 10050] Table 5 illustrates qualifiers that showed elevated or decreased signals when hybridized to AML samples as compared to MDS samples. Like Tables 1 and 3, the average hybridization signals at each qualifier for AML or MDS samples ("AML Average" and "MDS Average," respectively), the corresponding standard deviations ("AML StDev" and "MDS StDev," respectively), the ratios between the hybridized signals ("AML/MDS"), and the p-values for the observed differences are provided in Table 5. The genes represented by the qualifiers in Table 5 are further described in Table 6. 53 WO 2006/125195 PCT/US2006/019614 Table 3. Genes Differentially Expressed in MDS vs. Disease-Free PBMCs salifier MDS MDS StDev Disease-Free Disease-Free MDS/ P-value Average Average StDev Disease-Free (unequal) ?50_s at 241.6 201.6 9.31 13.71 25.95 5.65E-05 t411 at 30.9 31.78 1.78 1.29 17.38 6.12E-04 )672_at 70.65 70.68 4.91 4.73 14.39 5.33E-04 t33 s at 78.6 76.98 7.31 11.56 10.75 5.61E-04 i834 at 334.4 207.06 33.4 32.53 10.01 3.05E-06 167 s at 33.95 34.93 3.47 5.49 9.79 9.71E-04 i698_at 22.05 17.57 2.44 1.12 9.02 8.12E-05 ;592_at 61.65 57.77 6.96 8.47 8.86 4.53E-04 i60 s at 163.6 141.85 19.78 37.95 8.27 2.32E-04 27 x at 72.05 58.15 8.89 9.04 8.11 1.10E-04 15_x at 553.1 388 73.71 67.77 7.5 2.46E-05 66 s at 198.05 140.8 27 28.83 7.34 3.01E-05 '46 x at 57.85 44.1 7.93 7.23 7.29 6.91E-05 48 x at 577.4 370.97 85.67 86.93 6.74 O1.01E-05 19_xat 622.9 420.42 93.36 93.39 6.67 1.93E-05 502_at 25.2 20.07 3.89 3.01 6.48 1.40E-04 187_at 29.1 25.49 4.56 4.31 6.39 3.85E-04 01 s at 80.5 62.57 16.33 7.14 4.93 2.02E-04 974_at 87.75 61.02 19.13 8.34 4.59 7.45E-05 79_sat 105.1 80.58 23.8 8.25 4.42 2.39E-04 312_at 26.55 20.08 6.04 4.47 4.39 2.14E-04 748_at 136.05 105.05 31.22 20.87 4.36 2.70E-04 45 s at 14.9 12.51 3.42 2.08 4.35 6.12E-04 87_x_at 21.45 15.84 4.93 1.67 4.35 1.69E-04 886_at 17.15 14.71 4.04 1.48 4.24 8.00E-04 74 xat 15.15 10.84 3.64 2.07 4.16 1.42E-04 15 s at 9.3 7.36 2.27 0.89 4.1 4.11E-04 703_at 25.7 20.38 6.56 2.25 3.92 4.87E-04 12_s at 7.35 5.75 1.89 1.19 3.89 4.46E-04 83_xat 20.25 12.41 5.53 1.42 3.66 4.05E-05 61 sat 64.95 51.84 18.13 12.68 3.58 7.26E-04 546_at 4.55 3.09 1.29 0.46 3.53 1.48E-04 )77_at 15.5 10.61 4.42 2.67 3.51 1.69E-04 68 sat 10.6 7.97 3.07 1.07 3.46 4.60E-04 12 sat 57.3 46.47 16.64 6.54 3.44 9.47E-04 46_s at 82.35 48.24 24.38 5.32 3.38 3.45E-05 39 s at 6.35 4.68 1.89 0.91 3.36 4.30E-04 572_at 14.95 9.46 4.47 3.04 3.35 8.85E-05 19 sat 10.1 6.34 3.02 0.89 3.34 8.09E-05 12 sat 17.8 12.02 5.33 2.48 3.34 1.81E-04 54 WO 2006/125195 PCT/US2006/019614 ialifier MDS MDS StDev Disease-Free Disease-Free MDS/ P-value Average Average StDev Disease-Free (unequal) 595_s at 23 17.78 6.91 2.2 3.33 6.95E-04 644_at 5.9 4.17 1.78 0.42 3.32 2.92E-04 7144 at 42.8 29.19 13.42 5.97 3.19 2.48E-04 249_s at 47.65 28.24 14.96 5.87 3.19 5.33E-05 5202_at 6.65 4.07 2.16 0.47 3.09 9.09E-05 [042_at 6 4.39 1.96 0.47 3.07 5.84E-04 799 xat 14.75 11.41 4.82 1.51 3.06 9.93E-04 )86 s at 7.5 5.56 2.47 0.69 3.04 6.90E-04 )60x _at 26.85 15.64 8.87 2.46 3.03 5.78E-05 1252_at 11.3 7.6 3.76 1.23 3.01 2.82E-04 116_s at 6.35 4.51 2.13 0.5 2.98 5.10E-04 )404_at 10.3 6.78 3.51 2.2 2.93 2.70E-04 160_s _at 107.1 65.71 37.04 17.03 2.89 1.36E-04 [021 at 8.5 6.03 2.98 0.99 2.85 6.25E-04 1194_at 26 19.06 9.13 1.87 2.85 8.50E-04 )18 s at 18.45 12.92 6.58 1.78 2.8 6.02E-04 1236_at 4.75 3.45 1.71 0.46 2.78 8.82E-04 102 s at 52.35 26.53 18.87 9.09 2.77 1.85E-05 136_s at 206.25 135.61 74.42 17.42 2.77 3.49E-04 .307_at 8.65 5.84 3.2 0.84 2.7 5.23E-04 340_at 6 3.63 2.22 0.56 2.7 1.72E-04 806_at 52.8 31.8 19.58 5.29 2.7 1.67E-04 936_at 14.1 9.23 5.24 1.76 2.69 4.00E-04 ;23 x at 67.1 48.18 25.16 7.82 2.67 9.92E-04 177 at 6.45 3.28 2.42 0.66 2.66 2.69E-05 916_at 7.75 5.44 2.96 0.93 2.62 8.87E-04 57 s at 6.1 3.51 2.38 0.58 2.57 1.41E-04 96_x at 64.45 37.61 25.22 6.98 2.56 1.70E-04 99 sat 6.85 4.36 2.69 0.85 2.55 4.19E-04 ;84 s at 15.1 9.79 5.96 2.44 2.54 5.29E-04 117 at 33.35 20.72 13.18 3.29 2.53 3.46E-04 103 at 5.8 3.79 2.31 0.67 2.51 5.99E-04 18 s at 5.25 2.95 2.11 0.57 2.49 1.39E-04 .77 s at 20.25 12.05 8.16 4.57 2.48 2.68E-04 .26 sat 7.9 5.28 3.22 1.28 2.45 8.66E-04 945 at 10.15 6.14 4.2 1.1 2.42 3.63E-04 69 x at 8.1 4.7 3.36 0.83 2.41 2.40E-04 61 s at 50.9 19.72 21.18 2.92 2.4 1.86E-06 471 at 8.45 3.75 3.53 0.81 2.39 1.16E-05 441_at 11.05 7.23 4.62 1.51 2.39 8.30E-04 680 at 31.6 13.43 13.24 2.54 2.39 6.85E-06 52 s at 42.4 24.16 17.8 2.9 2.38 2.18E-04 43 s at 5.55 3.59 2.33 0.71 2.38 7.72E-04 55 WO 2006/125195 PCT/US2006/019614 DS MDisease-Free Disease-Free MDS/ P-value fier MDS StDev Average Average StDev Disease-Free (unequal) s-at 6.5 3.19 2.73 0.62 2.38 4.19E-05 x at 10.4 6.71 4.38 1.07 2.38 7.50E-04 )at 46.8 24.56 19.84 5.87 2.36 9.83E-05 at 7.95 3.71 3.4 0.89 2.34 2.64E-05 sat 5.4 3.52 2.31 0.85 2.34 9.33E-04 at 8.1 5.18 3.47 1.06 2.34 7.84E-04 s at 5.65 3.1 2.42 0.58 2.33 1.73E-04 )at 5.7 3.61 2.44 1.32 2.33 7.82E-04 s at 5.6 3.65 2.42 0.58 2.31 9.87E-04 5at 19.9 11.47 8.62 2.18 2.31 3.14E-04 at 4.75 2.94 2.07 0.62 2.3 6.42E-04 x at 10.2 6.29 4.44 1.14 2.3 6.30E-04 s-at 11 5.24 4.82 1.13 2.28 4.32E-05 s at 12.3 7.38 5.42 1.6 2.27 5.33E-04 s-at 46.95 29.62 20.76 6.1 2.26 8.71E-04 5at 4.9 3.06 2.18 0.78 2.25 8.34E-04 x at 4.4 2.52 1.98 0.4 2.22 3.94E-04 at 145.2 88.34 65.64 24.28 2.21 7.52E-04 s at 12.45 7.21 5.64 1.51 2.21 4.75E-04 x _at 14.15 7.5 6.42 2.47 2.2 1.99E-04 x at 6.7 2.7 3.04 1 2.2 7.18E-06 x at 7.6 2.93 3.47 0.89 2.19 4.22E-06 Iat 592.65 285.05 272.22 57.11 2.18 7.48E-05 at 14.95 8.79 6.93 1.71 2.16 6.51E-04 s_at 4.55 1.79 2.11 0.38 2.16 7.13E-06 s at 17.95 8.09 8.33 3.05 2.15 3.89E-05 x at 6.5 2.93 3.02 0.99 2.15 3.95E-05 s at 10.55 5.38 4.93 1.19 2.14 1.68E-04 s-at 69.85 41.61 33 7.54 2.12 8.54E-04 s at 11.9 6.54 5.62 1.23 2.12 4.02E-04 at 42.5 25.71 20.09 4.5 2.12 9.84E-04 at 6.9 4.02 3.27 1.16 2.11 7.39E-04 at 4.55 2.65 2.16 0.52 2.11 7.01E-04 s at 5.9 2.31 2.8 0.84 2.11 8.46E-06 at 4.8 2.46 2.29 0.55 2.1 2.17E-04 )_at 17.8 9.13 8.51 4.22 2.09 2.42E-04 xat 8.85 4.42 4.24 1.17 2.09 1.72E-04 s at 71.75 34.36 34.42 9.52 2.08 1.10E-04 x at 6.5 3.43 3.13 0.76 2.07 3.17E-04 s at 7.65 3.63 3.69 0.9 2.07 1.05E-04 at 6.45 2.42 3.11 1.01 2.07 5.44E-06 at 57.4 32.13 27.71 7.63 2.07 5.83E-04 sat 5.15 2.94 2.49 1.06 2.07 7.51E-04 56 WO 2006/125195 PCT/US2006/019614 MDS Disease-Free Disease-Free MDS/ P-value Average MDS StDev Average StDev Disease-Free (unequal) at 155.4 64.57 75.13 16.53 2.07 2.26E-05 at 7 3.24 3.4 0.99 2.06 8.73E-05 at 11.55 4.51 5.62 2.54 2.05 1.10E-05 at 5.6 2.68 2.73 0.75 2.05 1.33E-04 at 5 2.45 2.44 1.03 2.05 1.81E-04 at 7.75 3.18 3.82 0.96 2.03 2.40E-05 at 4.5 2.61 2.22 0.56 2.03 9.69E-04 at 10.65 4.34 5.27 1.05 2.02 2.35E-05 at 5.65 3.01 2.8 0.79 2.02 4.69E-04 at 6.25 2.94 3.11 1.01 2.01 1.34E-04 .at 49.4 22.88 24.62 6.68 2.01 1.15E-04 at 6 3.26 3 0.85 2 6.12E-04 at 3.8 3.04 7.6 3.95 0.5 1.08E-04 at 5.65 2.5 11.31 2.36 0.5 4.30E-10 at 4.35 2.32 8.71 2.18 0.5 2.93E-08 at 3.5 1.36 7.02 1.5 0.5 1.28E-11 at 4.2 2.31 8.44 1.91 0.5 4.19E-08 at 5.25 1.48 10.56 3.02 0.5 1.03E-13 at 9.45 5.44 19 6.51 0.5 2.26E-07 at 15.45 7.05 31.2 7.27 0.5 6.19E-10 at 26.3 11.07 53.16 16.23 0.49 3.06E-10 at 3.35 2.74 6.78 3.91 0.49 1.72E-04 at 3.6 1.47 7.29 2.38 0.49 2.97E-10 at 9.3 6.97 18.87 8.96 0.49 2.71E-05 at 5.4 1.73 10.96 2.58 0.49 4.58E-14 at 19.85 8.79 40.31 11.92 0.49 5.24E-10 at 3.45 1.61 7.02 1.95 0.49 9.79E-10 at 8.45 3.09 17.2 3.07 0.49 1.24E-12 at 17.65 8.37 36 14.7 0.49 3.14E-08 at 8.05 3.63 16.42 3.35 0.49 2.97E-10 at 21.65 14.78 44.18 16.48 0.49 2.52E-06 at 14.85 6.53 30.31 4.8 0.49 2.43E-10 at 8.25 2.88 16.87 2.92 0.49 2.62E-13 at 27.55 13.77 56.42 18.7 0.49 8.04E-09 at 4.35 3.25 8.91 5.04 0.49 5.73E-05 at 13.7 7.53 28.07 13.73 0.49 1.10E-06 at 2.75 1.65 5.64 3.27 0.49 1.32E-05 at 4.65 1.69 9.58 8.31 0.49 3.76E-04 at 8.9 3.32 18.38 4.61 0.48 1.49E-12 at 3.05 1.64 6.31 2.22 0.48 2.80E-08 at 12.2 5.38 25.33 6.15 0.48 7.00E-I I at 63.5 60.21 132.64 44.91 0.48 7.84E-05 at 8.35 2.85 17.44 2.9 0.48 4.02E-14 57 WO 2006/125195 PCT/US2006/019614 fer MDS M DS StDev Disease-Free Disease-Free MDS/ P-value fier MDS StDev Average Average StDev Disease-Free (unequal) s at 4.15 1.6 8.69 2.13 0.48 1.37E-12 s at 2.3 1.42 4.82 2.07 0.48 5.72E-07 x at 19.35 9.69 40.62 15.77 0.48 1.25E-08 s at 5.2 1.79 10.93 1.92 0.48 3.09E-14 ) at 17.95 11.54 37.76 9.28 0.48 1.56E-07 1 at 6.95 3.99 14.67 4.27 0.47 1.94E-08 s at 16.05 11.98 33.89 10.67 0.47 2.17E-06 9_at 5.6 2.6 11.84 4.34 0.47 1.61E-09 s at 23.55 16.03 49.91 17.47 0.47 5.77E-07 s at 27.85 27.37 59.04 20.05 0.47 8.45E-05 D at 22.9 20.16 48.56 17.67 0.47 2.46E-05 6_at 8.9 4.41 18.89 4.38 0.47 4.36E-10 s at 3.85 1.39 8.18 1.66 0.47 5.27E-14 s at 3.1 2.25 6.6 2.19 0.47 1.15E-06 s at 18.75 20.44 39.93 22.25 0.47 5.63E-04 s at 12.95 6.53 27.62 20.75 0.47 6.76E-05 1 at 25.3 16.44 53.98 16.51 0.47 1.46E-07 9 at 4.15 2.06 8.87 2.55 0.47 5.05E-10 s at 3.7 1.26 7.91 4.5 0.47 3.18E-07 2 at 7.25 3.16 15.58 5.53 0.47 2.01E-10 s at 3.05 2.37 6.56 2.89 0.47 6.25E-06 5 at 1.35 0.59 2.91 2.01 0.46 1.28E-05 4 at 11.35 5.61 24.51 7.87 0.46 5.47E-10 4 at 3.15 3.01 6.82 3.37 0.46 8.46E-05 s at 5.95 1.88 12.89 3.62 0.46 9.42E-15 s at 2.45 1.36 5.31 2.74 0.46 4.67E-07 x at 2.75 1.74 5.98 1.8 0.46 4.54E-08 s at 6.75 3.02 14.69 3.38 0.46 9.31E-12 0 at 5.1 2.02 11.11 2.16 0.46 2.77E-13 0 at 3.35 1.84 7.33 1.51 0.46 1.46E-09 s at 11.4 5.25 24.96 6.41 0.46 1.70E-11 s at 4.05 3.24 8.87 2.58 0.46 1.91E-06 s at 15.25 6.95 33.4 7.28 0.46 1.08E-11 s at 2.85 1.63 6.24 2 0.46 5.51E-09 6 at 5.75 4.44 12.62 3.54 0.46 9.74E-07 7_at 5.15 2.54 11.31 2.78 0.46 7.92E-11 s at 22.3 11.35 49.02 13.66 0.45 2.17E-10 2 at 7.95 4.26 17.49 6.3 0.45 2.92E-09 6_at 7.8 3.24 17.18 3.66 0.45 5.39E-13 x_at 11.4 10.19 25.16 11.83 0.45 2.20E-05 sat 5.4 5.45 11.93 5.59 0.45 8.08E-05 1_at 10.1 6.09 22.44 9.06 0.45 3.67E-08 9_at 25.5 20.85 56.96 26.6 0.45 5.50E-06 58 WO 2006/125195 PCT/US2006/019614 lifier MDS MDS StDev Disease-Free Disease-Free MDS/ P-value Average Average StDev Disease-Free (unequal) 6_xat 5.3 3.01 11.84 3.5 0.45 1.52E-09 54_at 10.2 4.92 22.8 5.3 0.45 1.79E-11 2 s at 4.3 1.63 9.64 2.62 0.45 4.34E-14 9.sat 2.05 1.1 4.6 1.98 0.45 1.06E-08 4_at 3.45 1.32 7.82 1.77 0.44 7.86E-15 08_at 17.45 11.69 39.62 11.95 0.44 2.65E-08 7 x at 11.15 3.82 25.33 6.58 0.44 1.02E-15 3 s at 25.7 26.6 58.4 26.75 0.44 5.41E-05 8 s at 1.55 0.51 3.53 2.41 0.44 2.70E-06 9_s_at 2.2 1.28 5.02 4.01 0.44 7.57E-05 5 s at 2.5 0.89 5.73 4.56 0.44 3.17E-05 9 s at 12.3 5.69 28.22 13.99 0.44 1.41E-08 I) s at 37.35 19.52 85.78 35.09 0.44 1.69E-09 54_at 2.35 1.18 5.4 1.6 0.44 2.82E-11 7_s at 4.4 1.73 10.11 2.43 0.44 1.14E-14 2_s at 6.7 3.26 15.4 3.77 0.44 6.12E-12 15_at 5.85 6.64 13.53 8.52 0.43 2.81E-04 , s at 5.25 4.92 12.18 7.16 0.43 3.60E-05 33_at 4.55 1.64 10,56 4.41 0.43 4.47E-11 ?4_at 2.45 1.23 5.69 1.82 0.43 3.17E-11 i6_at 20.55 11.73 47.98 13.2 0.43 2.16E-10 _xat 5.7 3.16 13.33 3.77 0.43 1.08E-10 _s-at 7.9 4.14 18.51 6.19 0.43 7.36E-11 )9 at 5.1 2.75 11.96 3.3 0.43 4.53E-11 _sat 5.65 3.12 13.29 4.34 0.43 1.51E-10 7_at 8 9.9 18.84 10.71 0.42 2.95E-04 )sat 2.75 1.29 6.49 2.41 0.42 2.96E-11 _sat 1.5 0.61 3.56 2.27 0.42 5.96E-07 sat 4.9 3.29 11.64 3.86 0.42 6.61E-09 _sat 2.6 1.47 6.2 1.56 0.42 5.57E-11 1 at 7.55 8.45 18.04 8.74 0.42 5.08E-05 2_at 3.6 1.54 8.73 2 0.41 5.69E-15 6 at 5.6 7.17 13.6 4.88 0.41 1.03E-04 _xat 4.9 3.78 12.07 2.98 0.41 2.34E-08 7_at 6.5 2.74 16.02 6.23 0.41 3.86E-12 9 at 6.6 2.41 16.31 6.72 0.4 5.17E-12 _sat 2.5 1.4 6.27 1.94 0.4 8.36E-12 3_at 6.5 5.06 16.31 3.6 0.4 1.62E-08 8_at 9.35 3.27 23.51 3.11 0.4 5.74E-18 _sat 2.45 0.69 6.2 2.2 0.4 7.16E-15 8_at 4.05 2.21 10.31 2.75 0.39 1.17E-12 _sat 18.95 7.05 48.53 8.16 0.39 2.63E-18 0_at 3 2.2 7.78 3 0.39 3.44E-09 59 WO 2006/125195 PCT/US2006/019614 ifier MDS MDS StDev Disease-Free Disease-Free MDS/ P-value Average Average StDev Disease-Free (unequal) 7 s at 3.15 1.46 8.18 2.17 0.39 3.61E-15 5 s at 14.6 12.27 38.51 13.32 0.38 1.67E-08 I-s at 5.55 2.16 14.73 4.12 0.38 2.60E-17 13 at 2 1.26 5.44 2.13 0.37 3.82E-11 72_at 2.2 2.02 6.02 5.11 0.37 5.67E-05 11 at 14.05 20.26 38.84 20.42 0.36 5.78E-05 Ss at 3.05 1.85 8.89 8.21 0.34 3.49E-05 ) s at 7.6 5.28 22.67 18.86 0.34 7.21E-06 16_at 7.1 2.99 21.42 5.15 0.33 2.07E-20 Z s at 4.2 8.7 14.02 12.01 0.3 5.19E-04 14_at 11.3 10.54 38.56 28.38 0.29 4.74E-07 )6_at 12.85 17.41 47.31 12.83 0.27 1.03E-08 i6_at 1.15 0.37 4.71 5.03 0.24 2.34E-05 18_at 5.95 13.64 34.69 35.17 0.17 1.29E-05 Table 4. Annotation of Genes Differentially Expressed in MDS vs. Disease-Free PBMCs ifier Symbol Name Unigene No Accession No. )s at CA1 carbonic anhydrase I Hs.23118 NM 001738 L _at IFI27 interferon, alpha-inducible protein 27 Hs.278613 NM 005532 72_at ERAF erythroid associated factor Hs.274309 NM016633 Is at SELENBP1 selenium binding protein 1 Hs.334841 NM 003944 14_at HBD hemoglobin, delta Hs.36977 NM 000519 7 s at SNCA synuclein, alpha (non A4 component of Hs.76930 NM 000345 amyloid precursor) )8_at XK Kell blood group precursor (McLeod Hs.78919 NM 021083 phenotype) solute carrier family 4, anion exchanger, )2_at SLC4A1 member 1 (erythrocyte membrane protein band Hs. 185923 X77737 3, Diego blood group) s at ALAS2 aminolevulinate, delta-, synthase 2 Hs.323383 AF130113 St (sideroblastic/hypochromic anemia) x at SNCA synuclein, alpha (non A4 component of Hs.76930 L36675 amyloid precursor) x at GARS, HBG1, glycyl-tRNA synthetase, hemoglobin, gamma Hs.283108 A1133353 HBG2 A, hemoglobin, gamma G s.30__5 s at SNCA synuclein, alpha (non A4 component of Hs.76930 BG260394 amyloid precursor) x at SNCA synuclein, alpha (non A4 component of Hs.76930 L36674 -xa -C amyloid precursor) ____L36 _x. at HBGl, HBG2 hemoglobin, gamma A, hemoglobin, gamma G Hs.266959 NM 000559 x at GARS, HBGI, glycyl-tRNA synthetase, hemoglobin, gamma Hs.283108 NM 000184 S HBG2 A, hemoglobin, gamma G 12_at BPGM 2,3-bisphosphoglycerate mutase Hs.198365 NM_001724 ;7_at GMPR guanosine monophosphate reductase Hs.1435 NM_006877 s at RNFO10 ring finger protein 10 Hs.5094 NM 014868 4_at MPP1 membrane protein, palmitoylated 1 (55kD) Hs.1861 NM 002436 s at BNIP3L BCL2/adenovirus E1B 19kD interacting Hs.132955 AF060922 protein 3-like _ _ _ A092 60 WO 2006/125195 PCT/US2006/019614 Ter Symbol Name Unigene No Accession No. at BCL2L1 BCL2-like 1 Hs.305890 AL117381 at LOC51094 CGI-45 protein Hs.5298 NM_015999 s at RALBP1 ralA binding protein 1 Hs.75447 NM_006788 x at TPM1 tropomyosin 1 (alpha) Hs.77899 M19267 at HIFO H1 histone family, member 0 Hs.226117 BC000145 x at MYL4 myosin, light polypeptide 4, alkali; atrial, Hs.356717 X52005 embryonic s at AP2B1 adaptor-related protein complex 2, beta 1 Hs.74626 AL567295 subunit _at PIN dynein, cytoplasmic, light polypeptide Hs.5120 NM_003746 s at SLC6A8 solute carrier family 6 (neurotransmitter Hs.187958 U41163 Transporter, creatine), member 8 CD59 antigen p18-20 (antigen identified by x at CD59 monoclonal antibodies 16.3A5, EJl6, EJ30, Hs.278573 BF983379 EL32 and G344) s at CSDA cold shock domain protein A Hs.198726 NM_003651 5 at BIKE homolog of mouse BMP-2 inducible kinase Hs.20137 NM_017593 7_at SEPX1 selenoprotein X, 1 Hs.279623 NM_016332 s at CTNNAL1 catenin (cadherin-associated protein), alpha- Hs.58488 NM 003798 like 1 s at GSPT1 G1 to S phase transition 1 Hs.2707 NM_002094 s at GABARAPL2 GABA(A) receptor-associated protein-like 2 Hs.6518 AB030710 s at ANK1 ankyrin 1, erythrocytic Hs.183805 AI659683 2 at AA654586 s at PINK1 PTEN induced putative kinase 1 Hs.6163 AF316873 s at HAGH hydroxyacyl glutathione hydrolase Hs.155482 NM_005326 s at NP nucleoside phosphorylase Hs.75514 NM_000270 at BIKE homolog of mouse BMP-2 inducible kinase Hs.20137 AI735391 4 at X04801 s at LOC81558 C/EBP-induced protein Hs.9851 NM 030802 2 at PCMT1 protein-L-isoaspartate (D-aspartate) O- Hs.79137 NM_005389 - methyltransferase 2 at AL031651 x at UBE2H ubiquitin-conjugating enzyme E2H (UBC8 Hs.28505 NM 003344 - - homolog, yeast) s at TPM1 tropomyosin 1 (alpha) Hs.77899 Z24727 x at EPB72 erythrocyte membrane protein band 7.2 Hs.160483 AI537887 (stomatin) 2 at RABI 13 RAB 13, member RAS oncogene family Hs.151536 NM 002870 s at TPM1 tropomyosin 1 (alpha) Hs.77899 NM 000366 4 at PROO611 PROO611 protein Hs.163833 NM_014076 s at CSDA cold shock domain protein A Hs.198726 AL556190 1 at SLPI secretory leukocyte protease inhibitor Hs.251754 NM 003064 -_ (antileukoproteinase) 4 at DKFZP566E144 small fragment nuclease Hs.7527 NM_015523 s at PINK1 PTEN induced putative kinase 1 Hs.6163 BF432478 6_at Hs.172405 AA166684 s at U08626 s at GPX1 glutathione peroxidase 1 Hs.76686 NM_000581 61 WO 2006/125195 PCT/US2006/019614 unlifier Symbol Name Unigene No Accession No. 1307_at FLJ10849 hypothetical protein FLJ10849 Hs.8768 AL534972 2340_at Hs.82719 BE673723 ?806_at H2B/S histone family member Hs.247817 BC000893 936 at TSTA3 tissue specific transplantation antigen P35B Hs.264428 U58766 323_xat OPHN1 oligophrenin 1 Hs.128824 NM 002547 )177_at DKFZP564J0123 DKFZP564J0123 protein Hs.31387 BC002873 3916_at SLC1A5 solute carrier family 1 (neutral amino acid Hs.183556 AF105230 Transporterr, member 5 357 s at PCMT1 protein-L-isoaspartate (D-aspartate) O- Hs.79137 M93008 methyltransferase 196 x at HDGF hepatoma-derived growth factor (high-mobility Hs.89525 NM 004494 group protein 1-like) 199 s at FLJ12806 hypothetical protein FLJ12806 Hs.107637 NM 022831 584 s at FLJ21588 ASC-1 complex subunit P100 Hs.334686 AL096741 S1117_at RBXI1 ring-box 1 Hs.279919 NM 014248 103_at BRD4 bromodomain-containing 4 Hs.278675 AI991631 118_sat DKFZP434N161 DKFZP434NI61 protein Hs.284208 NM_015493 177_s at Hs.177781 BF575213 126 s at RXRA retinoid X receptor, alpha Hs.20084 BE675800 1945_at ARG2 arginase, type II Hs.172851 NM_001172 769_x at TDE1 tumor differentially expressed 1 Hs.272168 BC006088 )61 s at EPB72 erythrocyte membrane protein band 7.2 Hs.160483 M81635 (stomatin) .471_at TDE1 tumor differentially expressed 1 Hs.272168 AW173623 441 at KEO4 similar to Caenorhabditis elegans protein Hs.285818 AL568449 C42C 1.9 Hs.28818 A56844 680 at PRDX1 peroxiredoxin 1 Hs.180909 L19184 vesicle-associated soluble NSF attachment 52 s at VTI2 protein receptor (v-SNARE; homolog of S. Hs.169206 AF035824 cerevisiae VTII) 43 s at CD34, FLJ00005 CD34 antigen, FLJ00005 protein Hs.367690 M81104 10 s at GRB10 growth factor receptor-bound protein 10 Hs.81875 AF000017 80_xat MGC2474, NXN hypothetical protein MGC2474, nucleoredoxin Hs.324709 NM023931 200_at CREG cellular repressor of EIA-stimulated genes Hs.5710 NM 003851 194_at CETN2 centrin, EF-hand protein, 2 Hs.82794 BC005334 sialyltransferase 7D ((alpha-N '37_s at SIAT7D acetylneuraminyl-2,3-beta-galactosyl-1,3)-N- Hs.3972 NM 014403 acetyl galactosaminide alpha-2,6 sialyltransferase) 106 at FLJ20489 hypothetical protein FLJ20489 Hs.306989 H14241 01_sat HOXB5 homeo box B5 Hs.22554 NM 002147 759_at TBCD tubulin-specific chaperone d Hs.12570 AW247323 91 sat GPX3 glutathione peroxidase 3 (plasma) Hs.336920 AW149846 155_at NCOR1 nuclear receptor co-repressor 1 Hs.144904 AA085748 733_at MYLE MYLE protein Hs.11902 NM 014015 63 x at FLJ12565 hypothetical protein FLJ12565 Hs.16036 NM_022064 CD59 antigen p18-20 (antigen identified by 84_sat CD59 monoclonal antibodies 16.3A5, EJ16, EJ30, Hs.278573 X16447 EL32 and G344) 62 WO 2006/125195 PCT/US2006/019614 lifier Symbol Name Unigene No Accession No. '9_sat LENG4 leukocyte receptor cluster (LRC) member 4 Hs.78768 BC003164 '5 s at BAG1 BCL2-associated athanogene Hs.41714 AF116273 26_at CCNF cyclin F Hs.1973 NM 001761 5_xat FLJ21736 hypothetical protein FLJ21736 Hs.268700 NM 024922 )5 at LOC91300 hypothetical protein BC012775 Hs.9739 W07773 2 s at AP2B1 adaptor-related protein complex 2, beta 1 Hs.74626 NM 001282 subunit 0_x_at AB025355 O_x_at HOXB5 homeo box B5 Hs.22554 A1052747 lxat SPN sialophorin (gpL1l5, leukosialin, CD43) Hs.80738 X60502 33_at UBB ubiquitin B Hs.183842 NM018955 71_at MAPK1 mitogen-activated protein kinase 1 Hs.324473 AA195999 5 s at KIAA0475 KIAA0475 gene product Hs.5737 BF115776 0 s at KIAA0102 KIAA0102 gene product Hs.77665 NM 014752 8xat GATA2, GATA binding protein 2, hypothetical protein Hs.760 BC002557 8_xat MGC2306 MGC2306 Hs.760 BC002557 3 s at PSMFI proteasome (prosome, macropain) inhibitor Hs.75925 NM 006814 subunit 1 (PI31) anti-oxidant protein 2 (non-selenium 4 s at AOP2 glutathione peroxidase, acidic calcium- Hs. 120 BE869583 independent phospholipase A2) 5 s at Hs.14846 AA148507 34_at LOC51024 CGI-135 protein Hs.84344 NM 016068 96_at SLC22A4 solute carrier family 22 (organic cation Hs.77239 NM 003059 transporter), member 4 99 at HT008 uncharacterized hypothalamus protein HT008 Hs.16206 NM 018469 1 s at MAPK1 mitogen-activated protein kinase 1 Hs.324473 NM_002745 73_at MLC1SA myosin light chain 1 slow a Hs.90318 NM 002475 50_at HEBP1 heme binding protein 1 Hs.294133 NM015987 2 x_ at TAGLN2, TPMT thiopurine S-methyltransferase, transgelin 2 Hs.75725 U12387 3 s at TALDOI1 transaldolase 1 Hs.77290 NM 006755 2_x_at Hs.372418 AK024108 6 s at CDK4 cyclin-dependent kinase 4 Hs.95577 NM 000075 )4_at POVI prostate cancer overexpressed gene 1 Hs. 18910 NM 003627 74_at ALOX5AP arachidonate 5-lipoxygenase-activating protein Hs.100194 NM_001629 7 s at C4S-2 chondroitin 4-O-sulfotransferase 2 Hs.25204 NM_018641 Is at NCOA4 nuclear receptor coactivator 4 Hs.99908 AL162047 2 s at FLJ23309 hypothetical protein FLJ23309 Hs.87128 NM 024896 5 s at CTBP2 C-terminal binding protein 2 Hs.171391 AF222711 l s at PYCS pyrroline-5-carboxylate synthetase (glutamate Hs.114366 NM 002860 gamma-semialdehyde synthetase) )4 at TGM3 transglutaminase 3 (E polypeptide, protein- Hs.2022 NM 003245 glutamine-gamma-glutamyltransferase) _x at SPN sialophorin (gpL115, leukosialin, CD43) Hs.80738 NM_003123 cysteine conjugate-beta lyase; cytoplasmic 17_at CCBL1 (glutamine transaminase K, kyneurenine Hs.46634 NM_004059 aminotransferase) )s at SRPKI SFRS protein kinase 1 Hs.75761 NM 003137 )_s at EMR2 egf-like module containing, mucin-like, Hs.137354 NM_013447 63 WO 2006/125195 PCT/US2006/019614 lifier Symbol Name Unigene No Accession No. hormone receptor-like sequence 2 10_at THTP thiamine triphosphate Hs.15098 NM 024328 Ix at SNX3 sorting nexin 3 Hs.12102 AF062483 9 s at HPS1 Hermansky-Pudlak syndrome 1 Hs.83951 NM 000195 6 s at NPR2L homologous to yeast nitrogen permease Hs.356137 NM_006545 (candidate tumor suppressor) 35_at ABT1 TATA-binding protein-binding protein Hs.109428 NM013375 34 at DDX8 DEAD/H (Asp-Glu-Ala-Asp/His) box Hs.171872 NM_004941 at DDX8 polypeptide 8 (RNA helicase) 1_sat ZNF278 zinc finger protein 278 Hs.27801 AF254083 7 s at KCNQ1 potassium voltage-gated channel, KQT-like Hs.156115 NM 000218 s a subfamily, member 1 5 s at C20orf34 chromosome 20 open reading frame 34 Hs.306044 NM 016408 0 s at LOC54103 hypothetical protein Hs. 12969 AK026747 57 at ICSBP1 interferon consensus sequence binding protein Hs.14453 A1073984 C I 5 s at MKNK2 MAP kinase-interacting serine/threonine kinase Hs.372455 NM 017572 2 9 x at MAP4K1 mitogen-activated protein kinase kinase kinase Hs.86575 BE646618 kinase 1 72 at U82828 9 s at DKFZP586F1318 hypothetical protein DKFZP586F1318 Hs.25213 NM 015677 3 s at HSU79252 hypothetical protein HSU79252 Hs.240062 AA046752 2 s at VIL2 villin 2 (ezrin) Hs.155191 AA670344 56_at TSFM Ts translation elongation factor, mitochondrial Hs.340959 AF110399 18_at BCL7B B-cell CLL/lymphoma 7B Hs.16269 NM_001707 7 s at FKBP11 FK506 binding protein 11 (19 kDa) Hs.24048 NM_016594 7 s at FDX1 ferredoxin 1 Hs.744 M18003 2 x at NR4A2 nuclear receptor subfamily 4, group A, member Hs.82120 NM_006186 2 5 s at SNRPA1 small nuclear ribonucleoprotein polypeptide A' Hs.80506 NM_003090 90 at DI3S106E highly charged protein Hs.151236 NM005800 31 at IRFI1 interferon regulatory factor 1 Hs.80645 NM_002198 I4x at DUSP1 dual specificity phosphatase 1 Hs.171695 AA530892 8 sat ARL7 ADP-ribosylation factor-like 7 Hs.111554 BC001051 20 at GTF3C1 general transcription factor IIIC, polypeptide 1 Hs.331 NM_001520 -_ _(alpha subunit, 220kD) 1 sat KIF5B kinesin family member 5B Hs.149436 BF223224 31 at CDR2 cerebellar degeneration-related protein (62kD) Hs.75124 AL582414 2_at Hs.52166 W05463 95 at Hs.71968 AL049265 37 _at FCNI ficolin (collagen/fibrinogen domain containing) Hs.252136 NM 002003 1 1 s at LOC51096 CGI-48 protein Hs.6153 NM_016001 1 s at GMEB2 glucocorticoid modulatory element binding Hs.28906 AL133646 protein 2 1 s at APBA2 amyloid beta (A4) precursor protein-binding, Hs.26468 AB014719 -_ -family A, member 2 (Xl I-like) 5_xat TCF7 transcription factor 7 (T-cell specific, HMG- Hs.169294 NM 003202 box) 0_s at NUP88 nucleoporin 88kD Hs.172108 NM 002532 64 WO 2006/125195 PCT/US2006/019614 qualifier Symbol Name Unigene No Accession No. 3320_at LNK lymphocyte adaptor protein Hs.13131 NM_005475 3931at ID2 inhibitor of DNA binding 2, dominant negative Hs.180919 A819238 helix-loop-helix protein 311 s at ARF6 ADP-ribosylation factor 6 Hs.89474 M57763 4429_at MTMR6 myotubularin related protein 6 Hs.79877 U47635 248 s at NR4A2 nuclear receptor subfamily 4, group A, member Hs.82120 877154 2 841 s at KLF4 Kruppel-like factor 4 (gut) Hs.356370 BF514079 1360_at CST3 cystatin C (amyloid angiopathy and cerebral Hs.135084 NM 000099 hemorrhage) 8486_at TIEG2 TGFB inducible early growth response 2 Hs.12229 AA149594 281 s _at PIGA phosphatidylinositol glycan, class A Hs.51 NM 002641 (paroxysmal nocturnal hemoglobinuria) s.1M026 271 s at UNC119 unc-119 homolog (C. elegans) Hs.81728 NM_005148 HLA-DQA1 major histocompatibility complex, class II, DQ 671_s at HLA-DQA2 alpha 1, major histocompatibility complex, Hs.198253 BG397856 class II, DQ alpha 2 961_s at COPEB core promoter element binding protein Hs.285313 ABO017493 )031 at CD3Z CD3Z antigen, zeta polypeptide (TiT3 Hs.97087 J04132 -_ _ ~complex) 4369_at PIK3CA phosphoinositide-3-kinase, catalytic, alpha Hs.85701 NM 006218 polypeptide 534 s at UB3L3 ubiquitin-like 3 Hs.173091 AF044221 )092_at MAGOH mago-nashi homolog, proliferation-associated Hs.57904 AF067173 (Drosophila) 354 s at BAZ2A bromodomain adjacent to zinc finger domain, Hs.277401 AA788652 s at BAZ2A 2A 1905_at CYLD cylindromatosis (turban tumor syndrome) Hs. 18827 BF516433 1794_at DUSP2 dual specificity phosphatase 2 Hs. 1183 NM 004418 3624_at ASM3A acid sphingomyelinase-like phosphodiesterase Hs.42945 AA873600 )68 s at DYRK2 dual-specificity tyrosine-(Y)-phosphorylation Hs.173135 Y09216 regulated kinase 2 170 s at HNRPH1 heterogeneous nuclear ribonucleoprotein HI Hs.245710 BF983406 (H) 576_x at SOS2 son of sevenless homolog 2 (Drosophila) Hs.348496 BF692958 965 s at HCNGP transcriptional regulator protein Hs.27299 NM 013260 1940 at FLJ13920 hypothetical protein FLJ13920 Hs.13056 NM 024558 [080_at FLJ13949 hypothetical protein FLJ13949 Hs.288198 NM 025077 )97_s at ZRF1 zuotin related factor 1 Hs.82254 AI338837 127 _s at HCLA-ISO hypothetical protein hCLA-iso Hs.143601 NM 030937 [81_s at RABGGTB Rab geranylgeranyltransferase, beta subunit Hs.78948 U49245 793_s at SCML1 sex comb on midleg-like 1 (Drosophila) Hs.109655 NM 006746 776 at PSMD11 proteasome (prosome, macropain) 26S subunit, Hs.90744 BF432873 non-ATPase, 11 .547_at CD4 CD4 antigen (p55) Hs.17483 U47924 )78 s at TCF8 transcription factor 8 (represses interleukin 2 Hs.232068 NM030751 expression) 032_at ZAP70 zeta-chain (TCR) associated protein kinase (70 Hs.234569 AI817942 kD) 396_at TCERG1 transcription elongation regulator 1 (CAl50) Hs.13063 NM 006706 23 x at HLA-DQBI major histocompatibility complex, class II, DQ Hs.73931 M17955 - -beta 1 11 s at C21orf7 chromosome 21 open reading frame 7 Hs.41267 NM 020152 65 WO 2006/125195 PCT/US2006/019614 ialifier Symbol Name Unigene No Accession No. 2861_at PER1 period homolog 1 (Drosophila) Hs.68398 NM 002616 1739_at SGK serum/glucocorticoid regulated kinase Hs.296323 NM 005627 326_x_at JUND jun D proto-oncogene Hs.2780 AI339541 3054_at MGC4701 hypothetical protein MGC4701 Hs.116771 BC003648 662 s _at FACL3 fatty-acid-Coenzyme A ligase, long-chain 3 Hs.268012 D89053 Hs.183418, 329 s at CDC2L1, cell division cycle 2-like 1 (PITSLRE Hs.214291, ALO31282 329sat CDC2L2 proteins), cell division cycle 2-like 2 Hs.355896 084_at CYLD cylindromatosis (turban tumor syndrome) Hs.18827 AI453099 phosphodiesterase 4B, cAMP-specific 3708_at PDE4B (phosphodiesterase E4 dunce homolog, Hs. 188 NM_002600 Drosophila) )77 xat SNRPA1 small nuclear ribonucleoprotein polypeptide A' Hs.80506 AJ130972 973 s at CEBPD CCAAT/enhancer binding protein (C/EBP), Hs.76722 NM 005195 s at delta 178 s at RBBP6 retinoblastoma binding protein 6 Hs.85273 NM 006910 959 s at KIAAO916 KIAA0916 protein Hs.151411 AA488899 555 s at FLJ20274 hypothetical protein FLJ20274 Hs.268371 NM_017736 319 s at MIR myosin regulatory light chain interacting Hs.20072 NM 013262 protein 920 sat BTG1 B-cell translocation gene 1, anti-proliferative Hs.77054 AL535380 7754 at KIAA0884, KIAA0884 protein, putative nucleolar RNA Hs.10098 NM 019082 S NOH61 helicase 557 s at HSF2 heat shock transcription factor 2 Hs.158195 M65217 142_s at UBE2G1 ubiquitin-conjugating enzyme E2G I (UBC7 Hs.78563 BC002775 142 sat B2Ghomolog, C. elegans) s.86B02 1345 at HCA1l2 hepatocellular carcinoma-associated antigen Hs.12126 NM 018487 112 512 sat VEGF vascular endothelial growth factor Hs.73793 AF022375 1783 at DKFZp761B2423 hypothetical protein DKFZp761B2423 Hs.91065 A1538172 7784 at YKT6 SNARE protein Ykt6 Hs.296244 BE384482 1756_at MGC17330 hypothetical protein MGC17330 Hs.26670 AL540260 751 xat JUND jun D proto-oncogene Hs.2780 AI762296 Z34 s _at VIL2 villin 2 (ezrin) Hs.155191 AF199015 )099 at Cl2orf5 chromosome 12 open reading frame 5 Hs.24792 NM 020375 ) 1 sat BRD2 bromodomain containing 2 Hs.75243 S78771 037 at DTR diphtheria toxin receptor (heparin-binding Hs.799 M60278 epidermal growth factor-like growth factor) phosphodiesterase 4D, cAMP-specific 140 s at PDE4D (phosphodiesterase E3 dunce homolog, Hs. 172081 U50157 Drosophila) 126 s at ID3 inhibitor of DNA binding 3, dominant negative Hs.76884 NM 002167 26_sa I3helix-loop-helix protein 113 s _at DEFCAP death effector filament-forming Ced-4-like Hs.104305 AF310105 apoptosis protein tumor necrosis factor receptor superfamily, 141 sat TNFRSF12 member 12 (translocating chain-association Hs.180338 U94510 membrane protein) 321 at EIF2S3 eukaryotic translation initiation factor 2, Hs.211539 NM 001415 -_______ ___subunit 3 (gamma, 52kD) _ 01 1142_at CYLD cylindromatosis (turban tumor syndrome) Hs.18827 AK024212 566_at RNASE6 ribonuclease, RNase A family, k6 Hs.23262 NM 005615 66 WO 2006/125195 PCT/US2006/019614 alifier Symbol Name Unigene No Accession No. 62_xat NCOA3 nuclear receptor coactivator 3 Hs.225977 AF010227 957 at AF093680 similar to mouse Glt3 orD. malanogaster Hs.279818 NM 013242 at AF09 680transcription factor IIB H.78012 '359_at FLJ22635 hypothetical protein FLJ22635 Hs.288529 NM 025092 119 s at VIPR1 vasoactive intestinal peptide receptor 1 Hs.348500 NM 004624 .793_at KIAA0443 KIAA0443 gene product Hs.113082 NM014710 848_at AKAP8 A kinase (PRKA) anchor protein 8 Hs.25059 AL050160 84_s at RNMT RNA (guanine-7-) methyltransferase Hs.8086 AB020966 758_at Hs.373513 AW337510 90 s at LOC51202 hqp0256 protein Hs.284288 NM 016355 820_at AHR aryl hydrocarbon receptor Hs.170087 NM 001621 '87 s at SLC5A6 solute carrier family 5 (sodium-dependent Hs.321579 NM 021095 vitamin transporter), member 6 s.321579 NM021095 46 s at CPVL carboxypeptidase, vitellogenic-like Hs.95594 NM031311 44 s at ASK activator of S phase kinase Hs.152759 NM_006716 serine (or cysteine) proteinase inhibitor, clade 283_at SERPINF 1 F (alpha-2 antiplasmin, pigment epithelium Hs.173594 NM 002615 derived factor), member 1 072_at HNRPL heterogeneous nuclear ribonucleoprotein L Hs.2730 NM_001533 821_at DTR diphtheria toxin receptor (heparin-binding Hs.799 NM 001945 - ltTepidermal growth factor-like growth factor) Hs.799 NM001945 88 s at RGS1 regulator of G-protein signalling 1 Hs.75256 NM 002922 60 s at COPEB core promoter element binding protein Hs.285313 BE675435 696 at EIF2AK3 eukaryotic translation initiation factor 2-alpha Hs.102506 NM 004836 kinase 3 32 s at LR8 LR8 protein Hs.190161 NM 014020 834_at RGSI1 regulator of G-protein signalling 1 Hs.75256 S59049 506 at TGFBI transforming growth factor, beta-induced, Hs.118787 NM 000358 -_ _ ~68kD 666_at HLA-DRB4 major histocompatibility complex, class II, DR Hs.318720 U70544 beta 4 s.12U75 728 at HLA-DRB4 major histocompatibility complex, class II, DR Hs.318720 BC005312 -______ ~beta 4 s.17 B05 Table 5. Genes Differentially Expressed in AML vs. MDS PBMCs uaiirAML P-value qualifier AMLverage AML StDev MDS Average MDS StDev AML/MDS P-v(unequal)e Average (unequal) 948 s at 83 90.08 12.7 17.49 6.54 5.29E-05 709 s at 32.19 29.76 5.45 6.46 5.91 6.46E-06 3949at 74.97 74.62 12.95 17.99 5.79 2.44E-05 9905_at 21.08 26.23 3.8 5.36 5.55 4.65E-04 13 Ix at 12.31 15.08 2.5 2.42 4.92 4.87E-04 783_xat 7.31 8.23 1.65 1.42 4.43 2.64E-04 1416at 30.64 33.41 7.2 7.78 4.26 2.42E-04 418_s_at 9.78 6.97 3.15 3.07 3.1 9.23E-06 310_sat 29.44 18.39 9.55 7.82 3.08 7.33E-07 5674 at 15.97 13.11 5.25 7.03 3.04 2.05E-04 1417 at 38.19 27.63 12.85 12.2 2.97 1.72E-05 67 WO 2006/125195 PCT/US2006/019614 ualifier AaML AML StDev MDS Average MDS StDev AML/MDS P-value Average _(unequal) 8788 s._at 17.11 14.28 6.15 7.07 2.78 3.31E-04 01162 at 17.72 13.64 6.4 8.48 2.77 3.47E-04 05609 at 6.83 5.82 2.55 1.64 2.68 1.58E-04 03787_at 6.92 5.81 2.65 0.88 2.61 1.09E-04 01459 at 7.31 5.12 2.8 2.98 2.61 1.16E-04 1163 sat 19.17 12.42 7.4 6.44 2.59 2.07E-05 19218 at 4.86 4.24 1.9 0.79 2.56 2.21E-04 04168 at 9.67 5.87 3.9 2.15 2.48 2.88E-06 1970 s at 11.22 8.6 4.55 3.89 2.47 2.12E-04 5382 s at 46.89 39.19 19.25 19.8 2.44 9.38E-04 5996 s at 11.11 6.23 4.6 2.16 2.42 7.67E-07 04039_at 24.53 20.97 10.2 7.31 2.4 5.33E-04 0796 s._at 7 5.91 2.95 1.96 2.37 4.79E-04 14500 at 7.22 6.2 3.05 2.31 2.37 7.09E-04 1825 s at 11.22 8.13 4.75 3.26 2.36 1.07E-04 8313 sat 7.83 5.61 3.35 1.98 2.34 7.44E-05 1892 s at 41.5 26.91 17.85 21.46 2.32 7.60E-04 1015 s at 6.72 5.47 2.9 2.38 2.32 6.69E-04 03675 at 19.83 13.78 8.6 5.64 2.31 8.09E-05 12141_at 3.19 2.95 1.4 0.5 2.28 9.95E-04 1946 s at 17.81 9.45 8 5.58 2.23 9.87E-06 10365_at 8.78 5.84 3.95 2.76 2.22 1.07E-04 19007 at 5.33 3.59 2.4 0.75 2.22 2.80E-05 0806 s at 25.44 14.18 11.55 6.67 2.2 7.32E-06 10092_at 15.89 7.14 7.25 3.16 2.19 7.96E-08 17988_at 20.17 12.11 9.25 6.39 2.18 4.89E-05 31487 at 19.44 13.36 8.95 4.37 2.17 8.20E-05 0829 s at 6.28 5.19 2.9 1.33 2.16 6.22E-04 35769 at 3.89 3.18 1.8 0.62 2.16 4.65E-04 32546 at 49.39 24.62 22.95 10.97 2.15 1.04E-06 19551 at 11.97 7.82 5.6 3.93 2.14 1.63E-04 7370_x_at 4.92 2.6 2.3 1.03 2.14 2.34E-06 1014_s at 6.83 4.72 3.2 1.24 2.14 8.15E-05 Z009_sat 3.81 2.69 1.8 1.24 2.11 3.74E-04 11023 at 8.42 5.79 4 2.34 2.1 1.93E-04 )1952_at 12.81 10.38 6.1 2.94 2.1 7.49E-04 3129 s at 5.14 3.39 2.45 0.83 2.1 4.92E-05 3253 s _at 9.11 4.01 4.35 2.21 2.09 4.63E-07 )4082 at 10.89 8.83 5.2 2.65 2.09 8.19E-04 5885 s._at 8.33 5.61 4.05 2.01 2.06 1.44E-04 1501_s at 61.94 30.01 30.3 22.59 2.04 4.93E-05 1450 sat 4.58 2.38 2.25 1.07 2.04 6.07E-06 [713_x at 4.17 3.41 2.05 0.69 2.03 8.81E-04 68 WO 2006/125195 PCT/US2006/019614 uaiirAML P-value ualifier AMLverage AML StDev MDS Average MDS StDev AML/MDS P-v(unequal)e Average (unequal) 2175 s at 12.56 7.35 6.25 2.81 2.01 3.15E-05 32188 at 5.22 2.68 2.6 1.6 2.01 2.86E-05 32502_at 6.92 4.56 3.45 2.42 2 4.77E-04 30812_at 13.81 8.47 6.9 4.64 2 2.36E-04 8711 s at 2.67 0.93 5.35 2.54 0.5 1.56E-04 4197 s at 19.69 17.33 39.6 16.5 0.5 1.21E-04 1882 s at 3.03 1.06 6.15 2.91 0.49 1.30E-04 6785 s at 1.33 0.72 2.75 1.59 0.48 9.32E-04 2587 s at 3.28 1.45 6.8 3.74 0.48 5.24E-04 32207 at 20.22 16.82 42.55 23.83 0.48 8.54E-04 9452 s at 19.89 8.01 42.4 24.16 0.47 5.69E-04 5174 s at 2.78 2.04 6.05 3.56 0.46 8.27E-04 2083 sat 4.75 3.04 10.35 6.23 0.46 9.21E-04 1477 s at 9.17 6.71 20.25 12.05 0.45 7.98E-04 1393 s at 5.64 4.68 13.1 7.64 0.43 4.74E-04 32996 at 3.17 2.43 7.65 4.39 0.41 2.70E-04 34698 at 5.56 7.44 13.5 6.09 0.41 8.36E-05 )7072 _at 4.08 3.15 10.4 6.77 0.39 6.22E-04 2426 s _at 3.06 1.97 7.9 5.28 0.39 6.78E-04 35291_at 9.94 6.68 26.4 15.47 0.38 1.50E-04 S319 sat 14.28 7.53 39.9 29.17 0.36 9.51E-04 [4617 at 12.61 16.66 37.65 26.32 0.33 6.42E-04 10164 at 8.28 10.61 25.15 17.77 0.33 6.17E-04 3646 sat 4.36 5.93 13.55 9.33 0.32 4.51E-04 10075 at 7.44 4.88 24.1 19.01 0.31 9.73E-04 5495 s at 12.86 19.7 42.15 31.09 0.31 7.08E-04 7145_at 14.22 22.96 51.55 38.57 0.28 5.05E-04 1146 sat 30.83 37.74 140.55 115.79 0.22 4.79E-04 Table 6. Annotation of Genes Differentially Expressed in AML vs. MDS PBMCs 'ualifier Symbol Name Unigene No. Accession No. 948 s at MPO myeloperoxidase Hs.1817 J02694 .709 s at SCGF stem cell growth factor; lymphocyte secreted C- Hs.105927 BC005810 type lectin 13949_at MPO myeloperoxidase Hs.1817 NM_000250 9905 at HOXA9 homeo box A9 Hs. 127428 AI246769 131 _xat SCGF stem cell growth factor; lymphocyte secreted C- Hs.105927 NM 002975 type lectin 1783_x_at SCGF stem cell growth factor; lymphocyte secreted C- Hs.105927 D86586 type lectin Meisl, myeloid ecotropic viral integration site 1 1416 at MEIS3, SOX4 homolog 3 (mouse), SRY (sex determining region Hs.83484 BG528420 Y)-box 4 418 s at MEIS3, SOX4 Meisl, myeloid ecotropic viral integration site 1 Hs.83484 NM 003107 -__-__homolog 3 (mouse), SRY (sex determining region s 69 WO 2006/125195 PCT/US2006/019614 Qualifier Symbol Name Unigene No. Accession No. Y)-box 4 )1310 sat P311 P311 protein Hs.142827 NM_004772 !06674_at FLT3 fms-related tyrosine kinase 3 Hs.385 NM_004119 01417 _at AL136179 [18788 sat FLJ21080 hypothetical protein FLJ21080 Hs.8109 NM 022743 01162_at IGFBP7 insulin-like growth factor binding protein 7 Hs. 119206 NM_001553 05609 at ANGPT1 angiopoietin I Hs.2463 NM 001146 03787_at SSBP2 single-stranded DNA binding protein 2 Hs.169833 NM_012446 01459_at RUVBL2 RuvB-like 2 (E. coli) Hs.6455 NM_006666 11163 s at IGFBP7 insulin-like growth factor binding protein 7 Hs.119206 NM_001553 19218_at FLJ23058 hypothetical protein FLJ23058 Hs.98968 NM 024696 04168 at MGST2 microsomal glutathione S-transferase 2 Hs.81874 NM_002413 1970 s at NASP nuclear autoantigenic sperm protein (histone- Hs.243886 NM_002482 90 aA binding) Hs_4386_N_0048 5382 sat DF D component of complement (adipsin) Hs.155597 NM 001928 5996 s at AK2 adenylate kinase 2 Hs.171811 NM 013411 04039 at CEBPA CCAAT/enhancer binding protein (C/EBP), alpha Hs.76171 NM 004364 0796 s at MCL1 myeloid cell leukemia sequence 1 (BCL2-related) Hs.86386 BF594446 14500 at H2AFY H2A histone family, member Y Hs.75258 AF044286 1825 sat LOC51097 CGI-49 protein Hs.238126 AL572542 UDP-N-acetyl-alpha-D 8313 s _at GALNT7 galactosamine:polypeptide N- Hs.246315 NM 017423 acetylgalactosaminyltransferase 7 (GalNAc-T7) 1892 s at IMPDH2 IMP (inosine monophosphate) dehydrogenase 2 Hs.75432 NM_000884 1015_s at JUP junction plakoglobin Hs.2340 NM_021991 03675 at NUCB2 nucleobindin 2 Hs.3164 NM_005013 12141 at MCM4 MCM4 minichromosome maintenance deficient 4 Hs.154443 AA604621 (S. cerevisiae) 1946 s at CCT2 chaperonin containing TCP1, subunit 2 (beta) Hs.6456 AL545982 10365 at RUNXI runt-related transcription factor 1 (acute myeloid Hs.129914 D43967 SNleukemia 1; amll oncogene) 19007 at FLJ13287 hypothetical protein FLJ13287 Hs.53263 NM 024647 0806 sat HSPD1 heat shock 60kD protein 1 (chaperonin) Hs.79037 BE256479 10092_at MAGOH mago-nashi homolog, proliferation-associated Hs.57904 AF067173 (Drosophila) 17988 at HEllO enhancer of invasion 10 Hs.107003 NM 021178 31487_at CTSC cathepsin C Hs.10029 NM001814 0829 s at SSBP2 single-stranded DNA binding protein 2 Hs.169833 AF077048 )5769 at FACVL1 fatty-acid-Coenzyme A ligase, very long-chain 1 Hs.11729 NM 003645 )2546 _at VAMP8 vesicle-associated membrane protein 8 Hs.172684 NM 003761 2 t VA(endobrevin) _ 036 19551 at BMO40 uncharacterized bone marrow protein BMO40 Hs.26892 NM_018456 7370_xat FUS fusion, derived from t(12; 16) malignant Hs.99969 S75762 liposarcoma phosphoribosylaminoimidazole carboxylase, 1014_s_at PAICS phosphoribosylaminoimidazole Hs.117950 NM 006452 succinocarboxamide synthetase Z009 s at STIP1 stress-induced-phosphoprotein 1 (Hsp70/Hsp90- Hs.75612 AL553320 organizing protein) .52 A532 70 WO 2006/125195 PCT/US2006/019614 )ualifier Symbol Name Unigene No. Accession No. 1023 at PDHB pyruvate dehydrogenase (lipoamide) beta Hs.979 AL117618 )1952_at ALCAM activated leucocyte cell adhesion molecule Hs.10247 AA156721 3129 s at GCSH glycine cleavage system protein H (aminomethyl Hs.356054 AI970157 carrier) ___A91 3253 s at KIAA0433 KIAA0433 protein Hs.26179 NM 015216 )4082 at PBX3 pre-B-cell leukemia transcription factor 3 Hs.294101 NM 006195 5885 sat ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit Hs.40034 L12002 of VLA-4 receptor) $50l sat H2AFY H2A histone family, member Y Hs.75258 AF044286 1450 sat MSH6 mutS homolog 6 (E. coli) Hs.3248 D89646 1713 x at KIAA0101 KIAA0101 gene product Hs.81892 BC005832 Z175 s at AK2 adenylate kinase 2 Hs.171811 AL513611 )2188 at KIAA0095 KIAA0095 gene product Hs.155314 NM 014669 )2502 at ACADM acyl-Coenzyme A dehydrogenase, C-4 to C-12 Hs.79158 NM 000016 straight chain )0812._at CCT7 chaperonin containing TCP 1, subunit 7 (eta) Hs. 108809 NM 006429 3711 s at SDPR serum deprivation response (phosphatidylserine Hs.26530 NM 004657 1 s binding protein) 1197 s at RUNX3 runt-related transcription factor 3 Hs.170019 NM 004350 1882 s at TMEM8 transmembrane protein 8 (five membrane- Hs.288940 A1636233 _ spanning domains) 5785 s at KLRC2 killer cell lectin-like receptor subfamily C, Hs.177605 NM 002260 member 2 1587 s at AK1 adenylate kinase 1 Hs.76240 BC001116 )2207 at ARL7 ADP-ribosylation factor-like 7 Hs.111554 BG435404 vesicle-associated soluble NSF attachment 452_s_at VTI2 protein receptor (v-SNARE; homolog of S. Hs.169206 AF035824 cerevisiae VTI1) 5174 s at QPCT glutaminyl-peptide cyclotransferase (glutaminyl Hs.79033 NM 012413 cyclase) 1083_s at SEC14L1 SEC14-like 1 (S. cerevisiae) Hs.75232 AI017770 1477 s at Hs.177781 BF575213 [393 sat IGF2R insulin-like growth factor 2 receptor Hs.76473 NM 000876 12996 at POLD4 polymerase (DNA-directed), delta 4 Hs.82520 NM021173 )4698 at ISG20 interferon stimulated gene (20kD) Hs.183487 NM 002201 )7072 at IL18RAP interleukin 18 receptor accessory protein Hs.158315 NM 003853 ,426 s at RXRA retinoid X receptor, alpha Hs.20084 BE675800 )5291 at IL2RB interleukin 2 receptor, beta Hs.75596 NM 000878 1319 s at RGS10 regulator of G-protein signalling 10 Hs.82280 NM 002925 4617_at PRF1 perforin 1 (pore forming protein) Hs.2200 AI445650 0164 at GZMB granzyme B (granzyme 2, cytotoxic T- Hs.1051 J03189 lymphocyte-associated serine esterase 1) 1646 s at KLRF1 killer cell lectin-like receptor subfamily F, Hs.183125 NM_016523 member I s11M06 0075 at LOC51257 hypothetical protein LOC51257 Hs.132744 AF151074 495_sat GNLY granulysin Hs.105806 NM_006433 7145_at GNLY granulysin Hs.105806 M85276 pro-platelet basic protein (includes platelet basic 146 s at PPBP protein, beta-thromboglobulin, connective tissue- Hs.2164 R64130 activating peptide III, neutrophil-activating peptide-2) 71 WO 2006/125195 PCT/US2006/019614 [0051] The genes depicted in Tables 2, 4, and 6 were identified according to Affymetrix annotation. Genes that corresponds to the qualifiers in Tables 1, 3, and 5 can also be identified by BLAST searching the target sequences of these qualifiers against human genome sequence databases. Databases suitable for this purpose include, but are not limited to, the human genome database at National Center for Biotechnology Information (NCBI), Bethesda, MD. NCBI also provides BLAST programs, such as "blastn," for searching its sequence databases. A BLAST search of a gene that corresponds to a qualifier can be conducted using an unambiguous segment of the target sequence of the qualifier (i.e., a sequence segment that does not contain any unknown nucleotide residue). Gene(s) whose protein-coding sequence has significant sequence identity with the unambiguous segment (e.g., having at least 95%, 96%, 97%, 98%, 99%, or more sequence identity) can be identified. The RNA transcript (or the complement thereof) of the gene(s) thus identified can hybridize under stringent or nucleic acid array hybridization conditions to the PM probes of the qualifier. Accordingly, the qualifiers in Tables 1, 3, and 5 represent not only genes that are explicitly depicted in the tables, but also genes that are not listed but nonetheless can hybridize under stringent or nucleic acid array hybridization conditions to the PM probes of the qualifiers. [0052] As used herein, "stringent conditions" are at least as stringent as conditions G-L in Table 7. "Highly stringent conditions" are at least as stringent as conditions A-F in Table 7. For each condition, hybridization is carried out under the corresponding hybridization conditions (Hybridization Temperature and Buffer) for about four hours, followed by two 20-minute washes under the corresponding wash conditions (Wash Temp. and Buffer). 72 WO 2006/125195 PCT/US2006/019614 Table 7. Stringency Conditions Stringency Poly-nucleotide Hybrid Hybridization Wash Tem. Condition Hybrid Length (bp) I Temperature and Buffer and Buffer A DNA:DNA >50 65 0 C; lxSSC -or- 65 0 C; 0.3xSSC 42 0 C; lxSSC, 50% formamide B DNA:DNA <50 TB*; lxSSC TB*; 1xSSC C DNA:RNA >50 67 0 C; lxSSC -or- 67 0 C; 0.3xSSC 45 0 C; 1xSSC, 50% formamide D DNA:RNA <50 TD*; 1xSSC TD*; IxSSC E RNA:RNA >50 70 0 C; 1xSSC -or- 70 0 C; 0.3xSSC 50 0 C; 1xSSC, 50% formamide F RNA:RNA <50 TF*; 1xSSC Tf*; 1xSSC G DNA:DNA >50 65 0 C; 4xSSC -or- 65 0 C; lxSSC 42 0 C; 4xSSC, 50% formamide H DNA:DNA <50 TH*; 4xSSC TH*; 4xSSC I DNA:RNA >50 67 0 C; 4xSSC -or- 67 0 C; 1xSSC 45oC; 4xSSC, 50% formamide J DNA:RNA <50 Tj*; 4xSSC Tj*; 4xSSC K RNA:RNA >50 70 0 C; 4xSSC -or- 67 0 C; 1xSSC 50 0 C; 4xSSC, 50% formamide L RNA:RNA <50 TL*; 2xSSC TL*; 2xSSC 1: The hybrid length is that anticipated for the hybridized region(s) of the hybridizing polynucleotides. When hybridizing a polynucleotide to a target polynucleotide of unknown sequence, the hybrid length is assumed to be that of the hybridizing polynucleotide. When polynucleotides of known sequence are hybridized, the hybrid length can be determined by aligning the sequences of the polynucleotides and identifying the region or regions of optimal sequence complementarity. H: SSPE (1xSSPE is 0.15M NaC1, 10mM NaH 2

PO

4 , and 1.25mM EDTA, pH 7.4) can be substituted for SSC (1xSSC is 0.15M NaCl and 15mM sodium citrate) in the hybridization and wash buffers. TB* - TR*: The hybridization temperature for hybrids anticipated to be less than 50 base pairs in length should be 5-10 0 C less than the melting temperature (Tm) of the hybrid, where Tm is determined according to the following equations. For hybrids less than 18 base pairs in length, Tm(oC) = 2(# of A + T bases) + 4(# of G + C bases). For hybrids between 18 and 49 base pairs in length, Tm( 0 C) = 81.5 + 16.6(logloNa

+

) + 0.41(%G + C) - (600/N), where N is the number of bases in the hybrid, and Na is the molar concentration of sodium ions in the hybridization buffer (Na + for lxSSC = 0.165M). C. Prognosis, Diagnosis and Selection of Treatment of MDS, AML or Other Leukemias [0053] The leukemia disease genes of the present invention can be used for diagnosis and prognosis of MDS, AML or other leukemias. For example, the disease genes can be used to identify an MDS patient who is likely to progress to acute myelogenous leukemia (AML). The leukemia disease genes can also be used to evaluate the progression or effectiveness of a treatment of leukemia in a patient of 73 WO 2006/125195 PCT/US2006/019614 interest. Any type of leukemia can be assessed according to the present invention. Examples of these leukemias include, but are not limited to, AML, MDS, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and hairy cell leukemia. The diagnosis and prognosis typically involve comparison of the peripheral blood expression profile of one or more disease genes in the leukemia patient of interest to at least one reference expression profile. [00541 In one embodiment, the disease genes employed for diagnosis and prognosis are selected such that the peripheral blood expression profile of each disease gene is correlated with a class distinction under a class-based correlation analysis (such as the nearest-neighbor analysis), where the class distinction represents an idealized expression pattern of the selected genes in peripheral blood samples of leukemia patients who have different clinical outcomes. In many cases, the selected disease genes are correlated with the class distinction at above the 50%, 25%, 10%, 5%, or 1% significance level under a random permutation test. [00551 The disease genes can also be selected such that the average expression profile of each disease gene in peripheral blood samples of one class of leukemia patients is statistically different from that in another class of leukemia patients or disease-free humans. For instance, the p-value under a Student's t-test for the observed difference can be no more than 0.05, 0.01, 0.005, 0.001, or less. In addition, the disease genes can be selected such that the average peripheral blood expression level of each disease gene in one class of patients is at least 2-, 3-, 4-, 5-, 10-, or 20-fold different from that in another class of patients or disease-free humans. [0056] The expression profile of the leukemia disease gene(s) in a peripheral blood sample of a subject of interest can be compared to a reference expression profile of the same gene(s) for diagnosing or evaluating the progression or treatment of leukemia in the subject of interest. The reference expression profile can be prepared using the same type of peripheral blood samples (e.g., whole blood samples or blood samples comprising enriched un-fractionated PBMCs) as the peripheral blood sample of the subject of interest. Both expression profiles can be prepared using the same preparation procedure or methodology. As a consequence, for each component in the expression profile of the subject of interest, there is at least one 74 WO 2006/125195 PCT/US2006/019614 corresponding component in the reference expression profile. A reference expression profile can be pre-determined or pre-recorded. It can also be prepared concurrently with or after the determination of the expression profile of the subject of interest. Each expression profile employed in the present invention can have any format, such as a table format, a graphic format, or an electronic or digital format. [0057] A reference expression profile employed in the present invention typically includes or consists of values or ranges that are suggestive of the expression pattern of the leukemia disease gene(s) in peripheral blood samples of disease-free humans or patients having known leukemias. In one embodiment, a reference expression profile comprises the average expression levels of each of the leukemia disease gene(s) in peripheral blood samples of disease-free humans. In another example, a reference expression profile comprises the average expression levels of each of the leukemia disease gene(s) in peripheral blood samples of patients who have the leukemia being investigated. Any averaging method can be used, including but not limited to arithmetic means, harmonic means, average of absolute values, average of log-transformed values, and weighted average. [00581 The reference expression profiles may include a plurality of expression profiles, each of which represents the peripheral blood expression pattern of the disease gene(s) in a particular leukemia patient whose clinical outcome is known or determinable. For example, a reference expression profile may include two or more individual expression profiles, each of which represents the expression profile of the leukemia disease gene(s) in a peripheral blood sample of a different leukemia patient or disease-free volunteer. The expression profile of a subject of interest can be compared to these individual reference expression profiles using a pattern recognition algorithm, such as weighted voting, k-nearest neighbors, or support vector machines. [0059] A reference expression profile suitable for the invention may contain ranges for the expression levels of each leukemia disease gene employed. Each range can be selected to reflect variations in the expression levels of the corresponding gene in peripheral blood samples of disease-free humans or patients who have known leukemias. For instance, the range can be selected to be one standard deviation (or a multiple or fraction thereof) from the mean expression level 75 WO 2006/125195 PCT/US2006/019614 of the corresponding gene in peripheral blood samples of disease-free humans (or patients having a known leukemia). Where the expression level of the gene in a subject of interest falls within that range, a "similar" call can be made with respect to that gene. [0060] Other types of reference expression profiles can also be used in the present invention. For example, a numerical threshold can be used as a reference. [0061] The expression profile of the patient of interest and the reference expression profile(s) can be constructed in any form. In one embodiment, the expression profiles comprise the expression level of each disease gene used in outcome prediction. The expression levels can be absolute, normalized, or relative levels. Suitable normalization procedures include, but are not limited to, those used in nucleic acid array gene expression analyses or those described in Hill et al., (2001) Genome Biol., 2:research0055.1-0055.13. In one example, the expression levels are normalized such that the mean is zero and the standard deviation is one. In another example, the expression levels are normalized based on internal or external controls, as appreciated by those skilled in the art. In still another example, the expression levels are normalized against one or more control transcripts with known abundances in blood samples. In many cases, the expression profile of the patient of interest and the reference expression profile(s) are constructed using the same or comparable methodologies. [0062] In another embodiment, each expression profile being compared comprises one or more ratios between the expression levels of different disease genes. An expression profile can also include other measures that are capable of representing gene expression patterns. [0063] Peripheral blood samples suitable for the present invention include, but are not limited to, whole blood samples or samples comprising un-fractionated PBMCs. In many embodiments, peripheral blood samples comprising enriched un fractionated PBMCs are employed. By "enriched," it means that the percentage of PBMCs in a sample is higher than that in whole blood. In many cases, at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% of the cells in an enriched sample is PBMCs. Methods suitable for preparing enriched un-fractionated PBMCs include, but are not 76 WO 2006/125195 PCT/US2006/019614 limited to, Ficoll gradients centrifugation or cell purification tubes (CPTs). Other conventional methods can also be used to prepare enriched un-fractionated PBMCs. [0064] Construction of the expression profiles typically involves detection of the expression level of each disease gene used in the diagnosis or prognosis. Numerous methods are available for this purpose. For instance, the expression level of a gene can be determined by measuring the level of the RNA transcript(s) of the gene. Suitable methods include, but are not limited to, quantitative RT-PCT, Northern Blot, in situ hybridization, slot-blotting, nuclease protection assay, and nucleic acid array (including bead array). The expression level of a gene can also be determined by measuring the level of the polypeptide(s) encoded by the gene. Suitable methods include, but are not limited to, immunoassays (such as ELISA, RIA, FACS, or Western blot), 2-dimensional gel electrophoresis, mass spectrometry, or protein arrays. [00651 The expression profile of the leukemia disease gene(s) in a subject of interest can be determined by measuring the RNA transcript level of each of the gene(s) in a peripheral blood sample of the subject. Methods suitable for this purpose include, but are not limited to, quantitative RT-PCT, competitive RT-PCR, real time RT-PCR, differential display RT-PCR, Northern Blot, in situ hybridization, slot-blotting, nuclease protection assays, and nucleic acid arrays (including bead arrays). The expression profile of the leukemia disease gene(s) can also be determined by measuring the protein product level of each of the gene(s) in the peripheral blood sample of the subject of interest. Methods suitable for this purpose include, but are not limited to, immunoassays (e.g., ELISA (enzyme-linked immunosorbent assay), RIA (radioimmunoassay), FACS (fluorescence-activated cell sorter), Western Blot, dot blot, immunohistochemistry, or antibody-based radioimaging), protein arrays, high-throughput protein sequencing, two-dimensional SDS-polyacrylamide gel electrophoresis, and mass spectrometry. In addition, the biological activity (e.g., enzymatic activity or protein/DNA binding activity) of the protein product encoded by a leukemia disease gene can also be used to measure the expression level of the gene in a peripheral blood sample of interest. 77 WO 2006/125195 PCT/US2006/019614 10066] The expression profile the leukemia disease gene(s) can have any form. In one embodiment, the expression profile includes the expression level of each leukemia disease gene employed. Each expression level can be an absolute expression level, or a normalized or relative expression level. Methods suitable for normalizing expression levels of different genes include, but are not limited to, those described in Hill et al., (2001) Genome Biol., 2:research0055.1-0055.13, and Genechip® Expression Analysis - Data Analysis Fundamentals (Part No. 701190 Rev. 2, Affymetrix, Inc., 2002), both of which are incorporated herein by reference in their entireties. In one example, the expression level of each leukemia disease gene is normalized based on internal or external controls. The expression level of each leukemia disease gene can also be normalized against one or more control transcripts with known abundances in the samples used. [00671 The expression profile of the leukemia disease gene(s) can also include ratio or ratios between the expression levels of different leukemia disease genes (e.g., ratios between the expression levels of genes that are up-regulated in PBMCs of leukemia patients versus genes that are down-regulated). Ratios between the expression levels of leukemia disease genes versus non-leukemia disease genes can also be used to construct the expression profiles of leukemia disease genes. Other measures that are indicative of gene expression patterns can also be used to prepare gene expression profiles. [0068] The difference or similarity between the expression profile of a subject of interest and a reference expression profile can be determined by assessing the differences or similarities between the corresponding components in the two profiles. Methods suitable for this purpose include, but are not limited to, fold changes or absolute differences. In one example, the expression level of a leukemia disease gene in a subject of interest is considered similar to the corresponding reference level in the reference expression profile if the difference between the two levels is less than 50%, 40%, 30%, 20%, or 10% of the reference level. In another example, the expression level of a leukemia disease gene in a subject of interest is considered similar to the corresponding reference level in the reference expression profile if the former level falls within the standard deviation (or a multiple or fraction therefore) of the reference level. 78 WO 2006/125195 PCT/US2006/019614 [0069] The criteria for the overall similarity between the expression profile of a subject of interest and a reference expression profile can be selected such that the accuracy (the ratio of correct calls over the total of correct and incorrect calls) for leukemia diagnosis or assessment is relatively high. For instance, the similarity criteria can be selected such that the accuracy for leukemia diagnosis or assessment is at least 50%, 60%, 70%, 80%, 90%, or more. In one example, an overall similarity call is made if at least 50%, 60%, 70%, 80%, 90%, or more of the components in the expression profile of the subject of interest are considered similar to the corresponding components in the reference expression profile. Different components in the expression profiles may have the same or different weights in comparison. The gene expression-based methods can also be combined with other clinical tests to improve the accuracy of leukemia diagnosis or assessment. [0070] The weighted voting algorithm is capable of assigning a class membership to a subject of interest. See Golub et al., supra, and Slonim et al., supra. Software programs suitable for this purpose include, but are not limited to, the GeneCluster 2 software (Broad Institute, Cambridge, MA). [0071] Under one form of the weighted voting analysis, a subject of interest is being assigned to one of two classes (i.e., class 0 and class 1), each class representing a different disease status (e.g., AML, MDS, or disease-free). For instance, class 0 can include disease-free humans and class 1 includes MDS (or AML) patients. For another instance, class 0 can include AML patients and class 1 includes MDS patients. A set of AML or MDS disease genes can be selected from Tables 2, 4, or 6 to form a classifier (i.e., class predictor). Each gene in the classifier casts a weighted vote for one of the two classes (class 0 or class 1). The vote of gene "g" can be defined as vg = ag (xg-bg), wherein ag equals to P(g,c) and reflects the correlation between the expression level of gene "g" and the class distinction between class 0 and class 1. bg equals to [x0(g) + xl(g)]/2, which is the average of the mean logs of the expression levels of gene "g" in class 0 and class 1. xg represents the normalized log of the expression level of gene "g" in the sample of interest. A positive vg indicates a vote for class 0, and a negative vg indicates a vote for class 1. V0 denotes the sum of all positive votes, and V1 denotes the absolute 79 WO 2006/125195 PCT/US2006/019614 value of the sum of all negative votes. A prediction strength PS is defined as PS = (VO - Vl)/(V0 + V I). [0072] Cross-validation can be used to evaluate the accuracy of a class predictor created under the weighted voting algorithm. In one embodiment, cross-validation includes withholding a sample which has been used in the neighborhood analysis for the identification of the disease genes. A class predictor is created based on the remaining samples, and then used-to predict the class of the sample withheld. This process is repeated for each sample that has been used in the neighborhood analysis. Class predictors with different leukemia disease genes are evaluated by cross validation, and the best class predictor with the most accurate predication can be identified. [0073] Any number of leukemia disease genes can be employed in the present invention. In one embodiment, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or more genes selected from Table 2 are used for the diagnosis or evaluation of the effectiveness of a treatment of AML in a subject of interest. In another embodiment, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or more genes selected from Table 4 are used for the diagnosis or evaluation of the effectiveness of a treatment of MDS in a subject of interest. In still another embodiment, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or more genes selected from Table 6 are used for the diagnosis or evaluation of the progression or treatment of MDS in a subject of interest. In a further embodiment, a combination of genes selected from Tables 2, 4, or 6 are used for the diagnosis or evaluation of the progression or treatment of AML or MDS in a subject of interest. [0074] The leukemia disease gene(s) employed in the present invention can be selected to have p-values of no greater than 0.05, 0.01, 0.005, 0.001, 0.0005, 0.0001, or less. The leukemia disease gene(s) can also be selected to include gene(s) that is upregulated in leukemia patients as compared to in disease-free humans, as well as gene(s) that is downregulated in leukemia patients as compared to in disease-free humans. To improve the accuracy of leukemia diagnosis or assessment, the leukemia disease gene(s) can also be selected through the use of optimization algorithms such as the mean variance algorithm as described in U.S. Patent Application 20040214179. 80 WO 2006/125195 PCT/US2006/019614 [0075] Where a weighted voting or k-nearest neighbors algorithm is used, the leukemia disease genes in a class predictor can be selected such that they are significantly correlated with the class distinction in the neighborhood analysis. For instance, the leukemia disease genes that are above the 1%, 5%, or 10% significance level in the neighborhood analysis can be selected. See Golub et al., supra, and Slonim et al., supra. The leukemia disease genes in a class predictor can also include top upregulated leukemia disease gene(s), as well as top downregulated leukemia disease gene(s). [0076] In one example, a class predictor employed in the present invention comprises or consists of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 40, or more genes selected from Table 2 or Table 4. The class predictor can include at least two groups of genes. The first group includes gene or genes having AML/Disease-Free ratios (or MDS/Disease-Free ratios) of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, and the second group includes gene or genes having AML/Disease Free ratios (or MDS/Disease-Free ratios) of no greater than 0.5, 0.333, 0.25, 0.2, 0.1, or less. [0077] In another example, a class predictor employed in the present invention comprises or consists of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 40, or more genes selected from Table 6. The class predictor can also include at least two groups of genes. The first group includes gene or genes having AML/MDS ratios of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, and the second group includes gene or genes having AML/MDS ratios of no greater than 0.5, 0.333, 0.25, 0.2, 0.1, or less. [0078] In addition to genes depicted in Tables 2, 4, and 6, the present invention also contemplates the use of other leukemia disease genes for the diagnosis or assessment of the progression or treatment of leukemia in a subject of interest. These genes can hybridize under stringent or nucleic acid array hybridization conditions to the qualifiers selected from Tables 2, 4, and 6. As used herein, a gene can hybridize to a qualifier if the RNA transcript (or the complement thereof, depending on the strandedness of the oligonucleotide probes of the qualifier) of the gene can hybridize to at least one oligonucleotide probe of the qualifier. In many instances, the RNA transcript (or the complement thereof) of the gene can hybridize under stringent or nucleic acid array hybridization conditions to at least 50%, 60%, 81 WO 2006/125195 PCT/US2006/019614 70%, 80%, 90% or 100% of the oligonucleotide probes of the qualifier and produce a "present" call at the qualifier on an Affymetrix Genechip® under the default settings (i.e., the threshold Tau is 0.015 and the significance level cal is 0.4). See Genechip® Expression Analysis - Data Analysis Fundamentals (Part No. 701190 Rev. 2, Affymetrix, Inc., 2002). D. Other Applications [0079] A clinical challenge concerning AML, MDS and other blood or bone marrow diseases is the highly variable response of patients to a therapy. The basic concept of pharmacogenomics is to understand a patient's genotype in relation to available treatment options and then individualize the most appropriate option for the patient. According to the present invention, different classes of patients can be created based on their different responses to a given therapy. Genes differentially expressed in un-fractionated PBMCs of one response class as compared to in another response class can be identified using the global gene expression analysis. These genes are molecular markers for predicting whether a patient of interest will be more or less responsive to the therapy. For patients predicted to have a favorable outcome, efforts to minimized toxicity of the therapy may be considered, whereas for those predicted not to respond to the therapy, treatment with other therapies or experimental regimes can be explored. [00801 In one embodiment, patients are grouped into at least two classes (class 0 and class 1). Class 0 includes patients who die within a specified period of time (such as one year) after initiation of a treatment. Class 1 includes patients who survive beyond the specified period of time after initiation of the treatment. Genes that are differentially expressed in un-fractionated PBMCs of class 0 patients as compared to in un-fractionated PBMCs of class 1 patients can be identified. These genes are prognostic markers of patient clinical outcome. Other clinical outcome criteria, such as remission/non-remission, time to progression, complete response, partial response, stable disease, or progressive disease, can also be used to group leukemia patients to identify the corresponding prognostic genes. 82 WO 2006/125195 PCT/US2006/019614 [0081] The leukemia disease genes of the present invention can also be used to identify or test drugs for the treatment of AML or MDS. The ability of a drug candidate to reduce or abolish the abnormal expression of AML or MDS disease genes in un-fractionated PBMCs is suggestive of the effectiveness of the drug candidate in treating AML or MDS. Methods for screening or evaluating drug candidates are well known in the art. These methods can be carried out either in animal models or during human clinical trials. [00821 The present invention also contemplates expression vectors encoding AML or MDS disease genes. These AML or MDS disease genes may be under expressed in AML or MDS tumor cells. By introducing the expression vectors into the patients in need thereof, abnormal expression of these genes can be corrected. Expression vectors and gene delivery techniques suitable for this purpose are well known in the art. [00831 In addition, this invention contemplates sequences that are antisense to AML or MDS disease genes or expression vectors encoding the same. The AML or MDS disease genes may be over-expressed in AML or MDS tumor cells. By introducing the antisense sequences or expression vectors encoding the same, abnormal expression of these disease genes can be corrected. [0084] Expression of an AML or MDS disease gene can also be inhibited by RNA interference ("RNAi"). RNAi is a technique used in post transcriptional gene silencing ("PTGS"), in which the targeted gene activity is specifically abolished. RNAi resembles in many aspects PTGS in plants and has been detected in many invertebrates including trypanosome, hydra, planaria, nematode and fruit fly (Drosophila melanogaster). It may be involved in the modulation of transposable element mobilization and antiviral state formation. RNAi in mammalian systems is disclosed in PCT application WO00/63364. In one embodiment, dsRNA of at least about 21 nucleotides is introduced into cells to silence the expression of the target gene. [0085] In addition, the present invention features antibodies that specifically recognize the polypeptides encoded by AML or MDS disease genes. These antibodies can be administered to patients in need thereof. In one embodiment, an antibody of the present invention can substantially reduce or inhibit the activity of a 83 WO 2006/125195 PCT/US2006/019614 disease gene. For instance, the antibody can reduce the activity of a disease gene by at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more. Suitable antibodies for the present invention include, but are not limited to, polyclonal antibodies, monoclonal antibodies, chimeric antibodies, humanized antibodies, single chain antibodies, Fab fragments, or fragments produced by a Fab expression library. In many embodiments, the antibodies of the present invention can bind to the respective AML or MDS disease gene products or other desired antigens with a binding affinity constant Ka of at least 106 M

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', 10 M-1, 108 M', 10 9 M-1, or more. [0086] A pharmaceutical composition comprising an antibody or a polynucleotide of the present invention can be prepared. The pharmaceutical composition can be formulated to be compatible with its intended route of administration. Examples of routes of administration include, but are not limited to, parenteral, intravenous, intradermal, subcutaneous, oral, inhalational, transdermal, topical, transmucosal, and rectal administration. Methods for preparing desirable pharmaceutical compositions are well known in the art. [0087] The present invention further features kits or apparatuses for diagnosing or monitoring the progression or treatment of AML or MDS. In one embodiment, a kit or apparatus of the present invention includes or consists essentially of one or more polynucleotides, each of which is capable of hybridizing under stringent conditions to a gene selected from Tables 2, 4, or 6. The polynucleotide(s) can be labeled with fluorescent, radioactive, or other detectable moieties. The polynucleotide(s) can be also un-labeled. Any number of polynucleotides can be included in a kit or apparatus. For instance, at least 1, 2, 3, 4, 5, 10, 15, 20, or more polynucleotides can be included in a kit or apparatus, each polynucleotide being capable of hybridizing under stringent conditions to a different respective gene selected from Tables 2, 4, or 6. In one example, the polynucleotide(s) included in a kit or apparatus is enclosed in a vial, a tube, a bottle or another containing mean. In another example, the polynucleotide(s) is stably attached to one or more substrates. Nucleic acid hybridization can be directly conducted on the substrate(s). Hybridization reagents can also be included in a kit or apparatus of the present invention. 84 WO 2006/125195 PCT/US2006/019614 [0088] In another embodiment, a kit or apparatus of the present invention includes or consists essentially of one or more antibodies specific for the polypeptide(s) encoded by the gene(s) selected from Tables 2, 4, or 6. The antibody or antibodies can be labeled with one or more detectable moieties to allow for detection of antibody-antigen complexes. The antibody or antibodies can also be un-labeled. [0089] Any number of antibodies can be included in a kit or apparatus. For instance, at least 1, 2, 3, 4, 5, 10, 15, 20, or more antibodies can be included in a kit or apparatus, and each of these antibodies can specifically recognize a different respective AML or MDS disease gene product. Immunodetection reagents (such as secondary antibodies, controls or enzyme substrates) can also be included in a kit or apparatus of the present invention. In one example, a kit of the present invention includes one or more containers which enclose the antibody or antibodies. In another example, the antibody or antibodies in an apparatus of the present invention are stably attached to one or more substrates. Substrates suitable for this purpose include, but are not limited to, films, membranes, column matrices, or microtiter plate wells. Immunoassays can be performed directly on the substrate(s). [0090] Furthermore, the present invention features systems capable of comparing an expression profile of interest to at least one reference expression profile. In many embodiments, the reference expression profiles are stored in a database. The comparison between the expression profile of interest and the reference expression profile(s) can be carried out electronically, such as by using a computer system. The computer system typically comprises a processor coupled to a memory which stores data representing the expression profiles to be compared. In one embodiment, the memory is readable as well as rewritable. The expression profiles can be retrieved or modified. The computer system includes one or more programs capable of causing the processor to compare the expression profiles. In one embodiment, the computer system includes a program capable of executing a weighted voting or a k-nearest-neighbors algorithm. In another embodiment, the computer system is coupled to a nucleic array from which hybridization signals can be directly fed into the system. 85 WO 2006/125195 PCT/US2006/019614 Kits for prognosis, diagnosis or selection of treatment ofMDS, AML, and other leukemias [0091] In addition, the present invention features kits useful for the prognosis, diagnosis or selection of treatment of MDS, AML or other leukemias. Each kit includes or consists essentially of at least one probe for a leukemia disease gene (e.g., a gene selected from Tables 2, 4, or 6). Reagents or buffers that facilitate the use of the kit can also be included. Any type of probe can be using in the present invention, such as hybridization probes, amplification primers, or antibodies. [0092] In one embodiment, a kit of the present invention includes or consists essentially of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more polynucleotide probes or primers. Each probe/primer can hybridize under stringent conditions or nucleic acid array hybridization conditions to a different respective leukemia disease gene. As used herein, a polynucleotide can hybridize to a gene if the polynucleotide can hybridize to an RNA transcript, or the complement thereof, of the gene. In another embodiment, a kit of the present invention includes one or more antibodies, each of which is capable of binding to a polypeptide encoded by a different respective leukemia disease gene. [00931 In one example, a kit of the present invention includes or consists essentially of probes (e.g., hybridization or PCR amplification probes or antibodies) for at least 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 or more genes selected from Table 2, 4 or 6. [0094] The probes employed in the present invention can be either labeled or unlabeled. Labeled probes can be detectable by spectroscopic, photochemical, biochemical, bioelectronic, immunochemical, electrical, optical, chemical, or other suitable means. Exemplary labeling moieties for a probe include radioisotopes, chemiluminescent compounds, labeled binding proteins, heavy metal atoms, spectroscopic markers, such as fluorescent markers and dyes, magnetic labels, linked enzymes, mass spectrometry tags, spin labels, electron transfer donors and acceptors, and the like. [0095] The kits of the present invention can also have containers containing buffer(s) or reporter means. In addition, the kits can include reagents for conducting positive or negative controls. In one embodiment, the probes employed in the 86 WO 2006/125195 PCT/US2006/019614 present invention are stably attached to one or more substrate supports. Nucleic acid hybridization or immunoassays can be directly carried out on the substrate support(s). Suitable substrate supports for this purpose include, but are not limited to, glasses, silica, ceramics, nylons, quartz wafers, gels, metals, papers, beads, tubes, fibers, films, membranes, column matrices, or microtiter plate wells. The kits of the present invention may also contain one or more controls, each representing a reference expression level of a disease gene detectable by one or more probes contained in the kits. [0096] It should be understood that the above-described embodiments and the following examples are given by way of illustration, not limitation. Various changes and modifications within the scope of the present invention will become apparent to those skilled in the art from the present description. E. Examples Example 1. Purification ofPBMCs and RNA [0097] Whole blood was collected from disease-free volunteers, patients with MDS, and patients with AML. Informed consents for the pharmacogenomic portions of these clinical studies were received and the project was approved by the local Institutional Review Boards at the participating clinical sites. MDS patients were primarily of Caucasian descent and had a mean age of 66 years (range of 52-84 years). AML patients were exclusively of Caucasian descent and had a mean age of 45 years (range of 19-65 years). Disease-free volunteers were exclusively of Caucasian descent with a mean age of 23 years (range of 18-32 years). [00981 Inclusion criteria for AML patients included blasts in excess of 20% in the bone marrow, morphologic diagnosis of AML according to the FAB classification system and flow cytometry analysis indicating CD33 + status. Inclusion criteria for MDS patients included morphologic diagnosis of MDS and FAB classification as refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, or refractory anemia with excess blasts in transformation (where disease stability had been demonstrated for a minimum of 2 months). 87 WO 2006/125195 PCT/US2006/019614 [0099] The blood samples were drawn into CPT Cell Preparation Vacutainer Tubes (Becton Dickinson). PBMCs were isolated over Ficoll gradients according to the manufacturer's protocol (Becton Dickinson). Total RNA was isolated from un fractionated PBMC pellets using Qiagen RNeasy ® mini-kits (Qiagen, Valencia, CA). Example 2. RNA Amplification and Generation of Genechip® Hybridization Probes [00100] Labeled target for oligonucleotide arrays was prepared using a modification of the procedure described in Lockhart et al., (1996) Nature Biotechnology 14:1675-1680. Two micrograms of total RNA were converted to cDNA using an oligo-d(T)24 primer containing a T7 DNA polymerase promoter at the 5' end. The cDNA was used as the template for in vitro transcription using a T7 DNA polymerase kit (Ambion, Woodlands, TX, USA) and biotinylated CTP and UTP (Enzo, Farmingdale, NY, USA). Labeled cRNA was fragmented in 40 mM Tris-acetate pH 8.0, 100 mM KOAc, 30 mM MgOAc for 35 min at 94 'C in a final volume of 40 pl. Example 3. Hybridization to Affymetrix Microarrays and Detection ofFluorescence [00101] Individual diseased and disease-free samples are hybridized to HG U133A Genechips® (Affymetrix). No samples are pooled. 10 ptg of labeled target is diluted in lx MES buffer with 100 jpg/ml herring sperm DNA and 50 pg/ml acetylated BSA. To normalize arrays to each other and to estimate the sensitivity of the oligonucleotide arrays, in vitro synthesized transcripts of 11 bacterial genes are included in each hybridization reaction, as described in Hill et al. (2000) Science 290:809-812. The abundance of these transcripts ranges from 1:300,000 (3 ppm) to 1:1000 (1000 ppm) stated in terms of the number of control transcripts per total transcripts. As determined by the signal response from these control transcripts, the sensitivity of detection of the arrays can range between about 1:300,000 and 1:100,000 copies/million. [00102] Labeled probes are denatured at 99 0 C for 5 minutes and then 45 0 C for 5 minutes and hybridized to oligonucleotide arrays comprised of over 12,500 human genes (HG-U133A, Affymetrix). Arrays are hybridized for 16 hours at 45 0 C. The hybridization buffer includes 100 mM MES, 1 M [Na+], 20 mM EDTA, and 0.01% 88 WO 2006/125195 PCT/US2006/019614 Tween 20. After hybridization, the cartridges is washed extensively with wash buffer 6x SSPET (e.g., three times at room temperature for at least 10 minutes each time). These hybridization and washing conditions are collectively referred to as "nucleic acid array hybridization conditions." The washed cartridges are subsequently stained with phycoerythrin coupled to streptavidin. [001031 12x MES stock contains 1.22 M MES and 0.89 M [Na ]. For 1000 ml, the stock can be prepared by mixing 70.4 g MES free acid monohydrate, 193.3 g MES sodium salt and 800 ml of molecular biology grade water, and adjusting volume to 1000 ml. The pH should be between 6.5 and 6.7. 2x hybridization buffer can be prepared by mixing 8.3 ml of 12x MES stock, 17.7 ml of 5 M NaCI, 4.0 ml of 0.5 M EDTA, 0.1 ml of 10% Tween 20 and 19.9 ml of water. 6x SSPET contains 0.9 M NaC1, 60 mM NaH 2

PO

4 , 6 mM EDTA, pH 7.4, and 0.005% Triton X-100. In some cases, the wash buffer is replaced with a more stringent wash buffer. 1000 ml of the stringent wash buffer can be prepared by mixing 83.3 ml of 12x MES stock, 5.2 ml of 5 M NaC1, 1.0 ml of 10% Tween 20 and 910.5 ml of water. Example 4. Gene Expression Data Analysis [00104] Data analysis and absent/present call determination are performed on raw fluorescent intensity values using Genechip® 3.2 software (Affymetrix). The "average difference" values for each transcript are normalized to "frequency" values using the scaled frequency normalization method in which the average differences for 11 control cRNAs with known abundance spiked into each hybridization solution were used to generate a global calibration curve. See Hill et al. (2001) Genome Biol., 2(12):research0055.1-0055.13, the entire content of which is incorporated herein by reference. This calibration is then used to convert average difference values for all transcripts to frequency estimates, stated in units of parts per million ranging from 1:300,000 (3 parts per million (ppm)) to 1:1000 (1000 ppm). [00105] Genechip® 3.2 software uses algorithms to calculate the likelihood as to whether a gene is "absent" or "present" as well as a specific hybridization intensity value or "average difference" for each transcript represented on the array. The 89 WO 2006/125195 PCT/US2006/019614 algorithms used in these calculations are described in the Affymetrix Genechip@ Analysis Suite User Guide. [00106] Specific transcripts can be evaluated further if they meet the following criteria. First, genes that are designated "absent" by the Genechip@ 3.2 software in all samples are excluded from the analysis. Second, in comparisons of transcript levels between arrays, a gene is required to be present in at least one of the arrays. Third, for comparisons of transcript levels between groups, a Student's t-test is applied to identify a subset of transcripts that had a significant difference (p < 0.05) in frequency values. In many cases, a fourth criterion, which requires that average fold changes in frequency values across the statistically significant subset of genes be 2-fold or greater, is also used. [00107] Unsupervised hierarchical clustering of genes and/or arrays on the basis of similarity of their expression profiles can be performed using the procedure described in Eisen et al. (1998) Proc. Nat. Acad. Sci. U.S.A., 95: 14863-14868. Nearest-neighbor prediction analysis and supervised cluster analysis can be performed using metrics illustrated in Golub et al., supra. For hierarchical clustering and nearest-neighbor prediction analysis, data can be first log-transformed and then normalized to have a mean value of zero and a variance of one. A Student's t-test can be used to compare disease-free, AML and MDS PBMC expression profiles. A p value of no more than 0.05 (e.g., no more than 0.01, 0.001, or less) can be used to indicate statistical significance. [00108] A k-nearest-neighbor's approach can be used to perform a neighborhood analysis of real and randomly permuted data using a correlation metric [P(g,c) = ([1-t2) / (al+ 02)], where g is the expression vector of gene g, c is a class vector, [l and 01 define the mean expression level and standard deviation of gene g in class 1, respectively, and t2 and o2 define the mean expression level and standard deviation of gene g in class 2, respectively. The measures of correlation for the most statistically significant genes observed in real class distinctions (AML versus disease-free, MDS versus disease-free, or AML versus MDS) can be compared to the most statistically significant measures of correlation observed in randomly permuted class distinctions. The top 1%, 5% and median distance measurements of 100 randomly permuted classes compared to the observed distance measurements 90 WO 2006/125195 PCT/US2006/019614 for AML versus disease-free, MDS versus disease-free, or AML versus MDS can be plotted to show the statistical verification of the leukemia disease genes identified by this invention. Example 5. Gene Classifiers for Prediction of Disease-Free versus MDS versus AML [00109] A 24-qualifier signature (8 cDNAs representing 7 genes defining AML, 8 cDNAs representing 7 genes defining MDS, and 8 cDNAs representing 8 genes defining disease-free) was identified. This signature can accurately predict and classify PBMC samples of disease-free individuals, MDS patients, or AML patients. This signature also identifies rapid MDS progressors as "AML," with implications for early detection of AML progression in MDS patients. [00110] The qualifiers in the 24-qualifier signature are listed in Table 8, below. For each qualifier, the signal-to-noise value associated with the qualifier is provided in the column labeled "Score." Each signal-to-noise value was greater than the value in the adjacent "Perm 1%" column, representing the signal-to-noise values observed for the top 1% of random permutations when the labels of the profiles were scrambled and then compared using identical class sizes. Thus, the actual signal-to noise values for the qualifiers were superior to those in the top 1% of random permutations. The corresponding human genes are identified by name, by symbol, by chromosomal location ("Cyto Band"), by Unigene number, and by GenBank accession number. Human genes used to identify AML include human myb; human neuronal protein 3.1; human myeloperoxidase; human catalase; human CGI-49; human stem cell growth factor; and human serine peptidase inhibitor, Kazal type 2 (acrosin-trypsin inhibitor). Human genes used to identify MDS include human NEDD4L; human glutathione peroxidase 3; human X-linked Kx blood group; human synuclein, alpha; human chromosome 8 open reading frame 5 1/hypothetical protein MGC3113; human interferon, alpha-inducible protein 27; and human transglutaminase 3. Human genes used to identify PBMCs from disease-free individuals include human chromosome 21 open reading frame 7; human amyloid beta A4 precursor protein-binding family A member 2; human KIAA0449; human F-box only protein 21; human death effector filament-forming ced-4-like apoptosis 91 WO 2006/125195 PCT/US2006/019614 protein; human zinc finger protein 14; human vasoactive intestinal peptide receptor 1; and human KIAA0443. [00111] Gene expression patterns in peripheral blood mononuclear cells were measured by oligonucleotide arrays for 45 disease-free subjects, 36 patients diagnosed with AML and 20 patients with initial diagnoses of MDS. Comparisons of these groups identified transcriptional differences that easily separated AML and MDS from healthy volunteers, and annotation revealed that many of the differences appeared due to proliferation of CD34 blasts in the circulation of these patients. The possibility of discriminating between MDS and AML patients on the basis of transcriptional profiles in peripheral blood was next explored. Of the 20 patients with initial diagnoses of MDS, six of the patient samples were determined to come from either 1) MDS patients with conflicting diagnoses between the site pathologist and a central pathologist (n=--3) or 2) MDS patients who rapidly progressed after blood sampling (< 3 months, n-3). A supervised approach on a training set of healthy, AML and non-progressor MDS samples was used to identify a gene classifier correlated with profiles in healthy individuals, stable MDS patients, and AML patients. An 8 gene classifier was optimally predictive, exhibiting an overall accuracy of 94 % in the training set (62/66 subjects correctly assigned by leave-one out cross validation). One of the four misclassified samples in the training set was from an MDS patient with a conflicting diagnosis who was "misclassified" upon cross validation as AML. When the 8 gene classifier was applied to the remaining samples in the test set, this classifier identified the remaining unambiguous samples in the test set with similar accuracy (87% overall accuracy of class assignment). This 8-gene predictor also assigned both samples from patients with conflicting diagnosis and all three samples from MDS patients with rapid times to disease progression as originating from patients with AML. These preliminary results imply that AML-like transcriptional profiles of MDS-diagnosed patients can precede standard clinical evidence of AML progression (e.g., blast hyperproliferation). The results from these studies indicate that the expression pattern of select transcripts in peripheral blood can provide early indicators of AML progression in leukemic patients with blast percentages that are commonly associated with a diagnosis of MDS. 92 WO 2006/125195 PCT/US2006/019614 Table 8. 24-qualifier classifier for AML, MDS, and normal PBMCs eDNA Accession SEQ ID Qualifier Unigene # Number NO: Name Symbol Cyto Band Score Pennrm 1% v-myb myeloblastosis viral oncogene homolog 204798 at Hs.591337 NM 005375 1 (avian) MYB 6q22-q23 2.21 1.0961764 201310 s at Hs.142827 NM 004772 3 P311 protein P311 5q21.3 1.71 0.9152079 203949 at Hs.1817 NM 000250 5 myeloperoxidase MPO 17q23.1 1.67 0.89075494 203948 s at Hs.1817 J02694 7 myeloperoxidase MPO 17q23.1 1.65 0.8588219 211922 s at Hs.502302 AY028632 9 catalase CAT 1p13 1.63 0.8588219 201825 s at Hs.498397 NM 016002 11 CGI-49 protein LOC51097 lq44 1.62 0.8539647 stem cell growth factor; lymphocyte secreted C-type 211709 s at Hs.512680 BC005810 13 lectin SCGF 19ql3.3 1.56 0.8351466 serine protease inhibitor, Kazal type, 2 (acrosin 206310 at Hs.98243 NM 021114 15 trypsin inhibitor) SPINK2 4qll 1.52 0.83016956 neural precursor cell expressed, developmentally down-regulated 4 212445 s at Hs.185677 BC032597 17 like NEDD4L 18q21 1.41 1.181725 glutathione peroxidase 3 214091 s at Hs.386793 NM 002084 19 (plasma) GPX3 5q23 1.31 1.0189847 Kell blood group precursor (McLeod 206698 at Hs.78919 NM 021083 21 phenotype) XK Xp21.1 1.28 1.0081878 synuclein, alpha (non A4 component of amyloid 204467 s at Hs.76930 NM 000345 23 precursor) SNCA 4q21 1.25 0.9812159 hypothetical protein 207458 at Hs.245886 NM 024035 25 MGC3113 MGC3113 8q24 1.22 0.97628 interferon, alpha 202411 at Hs.532634 NM 005532 27 inducible protein 27 IFI27 14q32 1.2 0.9383855 transglutaminase 3 (E polypeptide, protein-glutamine gamma glutamyltransferase 206004 at Hs.2022 NM 003245 29 ) TGM3 20qll.2 1.16 0.92764044 synuclein, alpha (non A4 component ofamyloid 211546 x at Hs.76930 L36674 31 precursor) SNCA 4q21 1.16 0.9226366 chromosome 21 open reading frame AL 221211 s at Hs.41267 NM 020152 33 7 C2lorf7 21q22.3 1.82 0.9432236 amyloid beta (A4) precursor protein binding, family A, member 2 (X11 AL 209871 s at Hs.525718 AB014719 35 like) APBA2 15q 1.65 0.8689916 AL 204411 at Hs.169182 NM 017596 37 KIAA0449protein KIAA0449 lpter-q31.3 1.52 0.85450727 F-box only protein AL 212229 s at Hs.159699 BC034045 39 21 FBXO21 12q24.21 1.42 0.85296124 death effector filament-forming Ced-4-like AL 210113 s at Hs.104305 AF310105 41 apoptosis protein DEFCAP 17pl3 1.4 0.8385079 zinc finger protein AL 219854 at Hs.197219 NM 021030 43 14 (KOX 6) ZNF14 19p13.3-p13.2 1.4 0.8292441 vasoactive intestinal peptide AL 205019 s at Hs.348500 NM 004624 45 receptor 1 VIPR1 3p22 1.37 0.82301474 KIAA0443 gene AL 204793 at Hs.113082 NM 014710 47 product KIAA0443 Xq22.1 1.34 0.8177944 93 WO 2006/125195 PCT/US2006/019614 [00112] The foregoing description of the present invention provides illustration and description, but is not intended to be exhaustive or to limit the invention to the precise one disclosed. Modifications and variations are possible in light of the above teachings or may be acquired from practice of the invention. Thus, it is noted that the scope of the invention is defined by the claims and their equivalents. 94^

Claims (49)

1. A method for diagnosis, or monitoring the occurrence, development, progression or treatment, of myelodysplastic syndromes (MDS), the method comprising the steps of: (1) generating a gene expression profile from a peripheral blood sample of a subject; and (2) comparing the gene expression profile to one or more reference expression profiles, wherein the gene expression profile and the one or more reference expression profiles comprise the expression patterns of one or more MDS disease genes in peripheral blood mononuclear cells (PBMCs), and wherein the difference or similarity between the gene expression profile and the one or more reference expression profiles is indicative of the presence, absence, occurrence, development, progression, or effectiveness of treatment of MDS in the subject.

2. The method of claim 1, wherein the peripheral blood sample comprises whole blood or enriched un-fractionated PBMCs.

3. The method of any one of the preceding claims, wherein the one or more MDS disease genes comprise one or more genes selected from Tables 4 or 6.

4. The method of any one of the preceding claims, wherein the one or more MDS disease genes comprise ten or more genes selected from Tables 4 or 6.

5. The method of any one of the preceding claims, wherein the one or more MDS disease genes comprise one or more MDS disease genes selected from Table 8.

6. The method of any one of the preceding claims, wherein the one or more reference expression profiles comprise a reference expression profile representing a disease-free human.

7. The method of any one of the preceding claims, wherein step (2) comprises comparing the gene expression profile to the one or more reference expression profiles by a k-nearest neighbor analysis or a weighted voting algorithm.

8. The method of any one of the preceding claims, further comprising the step of diagnosing or assessing MDS in the subject based on the comparison of step (2). 95 WO 2006/125195 PCT/US2006/019614

9. A method for diagnosis, or monitoring the occurrence, development, progression or treatment, of leukemia in a subject, the method comprising the steps of: (1) generating a gene expression profile from a peripheral blood sample from the subject; and (2) comparing the gene expression profile to one or more reference expression profiles, wherein the gene expression profile and the one or more reference expression profiles comprise the expression patterns of one or more leukemia disease genes selected from Table 4 or 6 in peripheral blood mononuclear cells (PBMCs), wherein the difference or similarity between the gene expression profile and the one or more reference expression profiles is indicative of the presence, absence, occurrence, development, progression, or effectiveness of treatment of leukemia in the subject, wherein the one or more leukemia disease genes are not recited in Table 2.

10. The method of claim 9, wherein the peripheral blood sample comprises whole blood or enriched un-fractionated PBMCs.

11. The method of claim 9 or 10, wherein the one or more leukemia disease genes comprise ten or more genes selected from Table 4 or 6.

12. The method of any one of claims 9-11, wherein the one or more leukemia disease genes selected from Table 4 or 6 comprise one or more genes also recited in Table 8.

13. The method of any one of claims 9-12, wherein the one or more reference expression profiles comprise a reference expression profile representing a disease free human.

14. The method of any one of claims 9-13, wherein step (2) comprises comparing the gene expression profile to the one or more reference expression profiles by a k nearest neighbor analysis or a weighted voting algorithm.

15. The method of any one of claims 9-14, wherein the leukemia is an acute myelogenous leukemia.

16. The method of any one of claims 9-14, wherein the leukemia is a myelodysplastic syndrome. 96 WO 2006/125195 PCT/US2006/019614

17. The method of any one of claims 9-16, further comprising the step of diagnosing or assessing leukemia in the subject based on the comparison of step (2).

18. A method for identifying an MDS patient who is likely to progress to acute myelogenous leukemia (AML), the method comprising the steps of: (1) generating a gene expression profile from a peripheral blood sample from an MDS patient; (2) comparing the gene expression profile to one or more reference expression profiles, wherein the gene expression profile and the one or more reference expression profiles comprise the expression patterns of one or more leukemia disease genes selected from Table 6 in peripheral blood mononuclear cells (PBMCs), wherein the difference or similarity between the gene expression profile and the one or more reference expression profiles is indicative that the MDS patient is likely to progress to AML.

19. The method of claim 18, wherein the one or more reference expression profiles comprises a reference expression profile representing an AML patient.

20. The method of claim 18 or 19, wherein the peripheral blood sample comprises whole blood or enriched un-fractionated PBMCs.

21. The method of any one of claims 18-20, wherein the one or more leukemia disease genes selected from Table 6 are also recited in Table 8.

22. An array for use in a method for diagnosing a myelodysplastic syndrome (MDS) comprising a substrate having a plurality of addresses, each address comprising a distinct probe disposed thereon, wherein at least 15% of the plurality of addresses have disposed thereon probes that can specifically detect MDS disease genes in peripheral blood mononuclear cells.

23. The array of claim 22, wherein at least 30% of the plurality of addresses have disposed thereon probes that can specifically detect MDS disease genes in peripheral blood mononuclear cells.

24. The array of claim 22, wherein at least 50% of the plurality of addresses have disposed thereon probes that can specifically detect MDS disease genes in peripheral blood mononuclear cells. 97 WO 2006/125195 PCT/US2006/019614

25. The array of any one of claims 22-24, wherein the MDS disease genes are selected from Table 4.

26. The array of any one of claims 22-25, wherein the probe is a nucleic acid probe.

27. The array of any one of claims 22-25, wherein the probe is an antibody probe.

28. An array for use in a method for diagnosis of leukemia comprising a substrate having a plurality of addresses, each address comprising a distinct probe disposed thereon, wherein at least 15% of the plurality of addresses have disposed thereon probes that can specifically detect genes selected from Tables 4 or 6, wherein the genes are not recited in Table 2.

29. The array of claim 28, wherein at least 30% of the plurality of addresses have disposed thereon probes that can specifically detect genes selected from Tables 4 or 6, wherein the genes are not recited in Table 2.

30. The array of claim 28, wherein at least 50% of the plurality of addresses have disposed thereon probes that can specifically detect genes selected from Tables 4 or 6, wherein the genes are not recited in Table 2.

31. The array of any one of claims 28-30, wherein the probe is a nucleic acid probe.

32. The array of any one of claims 28-30, wherein the probe is an antibody probe.

33. A computer-readable medium comprising a digitally-encoded expression profile comprising a plurality of digitally-encoded expression signals, wherein each of the plurality of digitally-encoded expression signals comprises a value representing the expression of a gene selected from Tables 4 or 6, wherein the gene is not recited in Table 2.

34. The computer-readable medium of claim 33, wherein the value represents the expression of the gene in a peripheral blood mononuclear cell of a patient with a myelodysplastic syndrome (MDS).

35. The computer-readable medium of claim 33, wherein the value represents the expression of the gene in a peripheral blood mononuclear cell of a patient with acute myelogenous leukemia (AML). 98 WO 2006/125195 PCT/US2006/019614

36. The computer-readable medium of claim 33, wherein the digitally-encoded expression profile comprises at least ten digitally-encoded expression signals.

37. A kit for diagnosis of a myelodysplastic syndrome (MDS), the kit comprising: a) one or more probes that can specifically detect MDS disease genes in peripheral blood mononuclear cells; and b) one or more controls, each representing a reference expression level of an MDS disease gene detectable by the one or more probes.

38. The kit of claim 37, wherein the MDS disease genes are selected from Table 4.

39. The kit of claim 38, wherein the MDS disease genes selected from Table 4 are also recited in Table 8.

40. A kit for diagnosis of leukemia, the kit comprising: a) one or more probes that can specifically detect genes selected from Tables 4 or 6, wherein the genes are not recited in Table 2; and b) one or more controls, each representing a reference expression level of a disease gene detectable by the one or more probes.

41. The kit of claim 40, wherein the genes selected from Tables 4 or 6 are also recited in Table 8.

42. A method of making a decision regarding an individual, the method comprising the step of: assigning the individual to a class based on a value that is a function of the expression, in a peripheral blood sample from the individual, of one or more genes selected from Tables 4 or 6, wherein the genes are not recited in Table 2, thereby making a decision regarding the individual.

43. The method of claim 42, wherein the one or more genes selected from Tables 4 or 6 are also recited in Table 8.

44. The method of claim 42 or 43, wherein the decision is recorded.

45. The method of claim 44, wherein the decision is recorded in a computer readable medium.

46. The method of any one of claims 42-45, wherein the method further includes selecting a leukemia treatment based on the assignment. 99 WO 2006/125195 PCT/US2006/019614

47. The method of any one of claims 42-46, wherein the method further includes administering a leukemia treatment based on the assignment.

48. The method of any one of claims 42-47, wherein the method further includes issuing, transmitting or receiving a prescription for a leukemia treatment based on the assignment.

49. The method of any one of claims 42-48, wherein the method further includes authorizing, paying for, or causing a transfer of funds to pay for a leukemia treatment based on the assignment. 100