Diagnosis, prognosis and identification of potential therapeutic targets of multiple myeloma based on gene expression profiling
First Claim
1. A method of diagnosis for subgroups of multiple myeloma, comprising the steps of:
- isolating plasma cells from an individual; and
examining expression of a group of 24 genes within the plasma cells, said 24 genes having accession numbers X54199, M20902, X89985, M31158, U44111, X16416, HT2811, D16688, U57316, U77456, D13645, M64590, L77701, U20657, L06175, M26311, X04366, AC002115, X06182, M16279, M97676, U10324, S85655, and X63692; and
performing statistical analysis on the expression levels of the genes, wherein a statistically significant value of the analysis provides diagnosis for subgroups of multiple myeloma.
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Abstract
Provided herein are methods for diagnosing and treating multiple myeloma based on statistical analysis of and subsequent increasing/inhibiting expression of subgroups of plasma cells and B cell genes. Also provided are methods for a developmental stage-based classification for multiple myeloma using hierarchical clustering analysis of plasma cell and B cell nucleic acids and for discriminating among normal, hyperplastic and malignant using gene expression array data and statistical analysis thereof. In addition methods for determining the risk of developing bone disease in a test individual by examining expression levels of a WNT signaling antagonist, such as DKK1, are provided. A kit comprising anti-DKK1 antibodies and detection reagents for measuring DKK1 protein levels also is provided.
73 Citations
20 Claims
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1. A method of diagnosis for subgroups of multiple myeloma, comprising the steps of:
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isolating plasma cells from an individual; and examining expression of a group of 24 genes within the plasma cells, said 24 genes having accession numbers X54199, M20902, X89985, M31158, U44111, X16416, HT2811, D16688, U57316, U77456, D13645, M64590, L77701, U20657, L06175, M26311, X04366, AC002115, X06182, M16279, M97676, U10324, S85655, and X63692; and performing statistical analysis on the expression levels of the genes, wherein a statistically significant value of the analysis provides diagnosis for subgroups of multiple myeloma. - View Dependent Claims (2)
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3. A method of treatment for multiple myeloma, comprising:
inhibiting expression of a gene that has an accession number U09579, U78525, HT5158, X57129, M55210, L77886, U73167, X16416, U57316, Y09022, M25077, AC002115, Y07707, L22005, X66899, D50912, HT4824, U10324, AD000684, U68723, X16323, U24183, D13645, S85655, X73478, L77701, U20657, M59916, D16688, X90392, U07424, X54199, L06175, M55267, M87507, M90356, U35637, L06845, U81001, U76189, U53225, X04366, U77456, L42379, U09578, Z80780, HT4899, M74088, X57985, X79882, X77383, M91592, X63692, M60752, M96684, U16660, M86737, U35113, X81788, HT2217, M62324, U09367, X89985, L19871, X69398, X05323, X04741, D87683, D17525, M64347, U89922, X67325, X59798, U62800, U35340, X12530, X59766, U58096, U52513, X76223, X92689, D17427, L11329, L13210, U10991, L10373, U60873, M65292, HT4215, D13168, AC002077, M92934, X82494, M30703, U9103, or NM012242.
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4. A method of treatment for multiple myeloma, comprising:
increasing expression of a gene that has an accession number L36033, M63928, U64998, M20902, M26602, M21119, M14636, M26311, M54992, X16832, M12529, M15395, Z74616, HT2152, U97105, U81787, HT3165, M83667, L33930, D83657, M11313, M31158, U24577, M16279, HT2811, M26167, U44111, X59871, X67235, U19713, Y08136, M97676, M64590, M20203, M30257, M93221, S75256, U97188, Z23091, M34344, M25897, M31994, Z31690, S80267, or U00921.
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5. A method of developmental stage-based classification for multiple myeloma, comprising the steps of:
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(a) isolating plasma cells and B cells from normal individuals; (b) isolating nucleic acid samples from the plasma cells and B cells; (c) hybridizing the nucleic acid samples to a DNA microarray; (d) performing hierarchical clustering analysis on data obtained from the hybridization, wherein the clustering analysis will identify genes that classify the plasma cells and B cells according to their developmental stages; (e) isolating multiple myeloma plasma cells from individuals with multiple myeloma; (f) isolating nucleic acid samples from the multiple myeloma plasma cells; (g) hybridizing nucleic acid samples of (f) to a DNA microarray; and (h) performing hierarchical clustering analysis on data obtained from (d) and (g), wherein the clustering analysis classifies the multiple myeloma plasma cells according to the developmental stages of normal B and plasma cells.
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7. A method of discriminating normal, hyperplastic and malignant plasma cells, comprising the steps of:
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obtaining gene expression data by DNA microarray; and performing statistical analysis on the data by logistic regression, decision trees, ensembles, naï
ve bayes, bayesian networks, or support vector machines, wherein the analysis discriminates among normal, hyperplastic and malignant plasma cells. - View Dependent Claims (8, 13, 14)
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9. A method of determining the risk of developing bone disease in a test individual, comprising:
examining the expression level of a WNT signaling antagonist in said test individual, wherein increased expression of said antagonist compared to that in normal individual indicates that said test individual has or is at risk for developing bone disease. - View Dependent Claims (6, 10, 11, 12, 15, 16, 17, 18, 19)
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20. A kit for measuring the level of DKK1 protein in a biological sample, said kit comprising anti-DKK1 antibodies and reagents for detecting the antibodies.
Specification