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Development of gene expression-based score to predict sensitivity of multiple myeloma cells to DNA methylation inhibitors
- Source :
- Molecular Cancer Therapeutics, Molecular Cancer Therapeutics, American Association for Cancer Research, 2012, 11 (12), pp.2685-92. ⟨10.1158/1535-7163.MCT-12-0721⟩
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 2012.
-
Abstract
- Multiple myeloma is a plasma cell cancer with poor survival, characterized by the clonal expansion of multiple myeloma cells (MMC), primarily in the bone marrow. Novel compounds are currently tested in this disease, but partial or minor patients' responses are observed for most compounds used as a single agent. The design of predictors for drug efficacy could be most useful to better understand basic mechanisms targeted by these drugs and design clinical trials. In the current study, we report the building of a DNA methylation score (DM score) predicting the efficacy of decitabine, an inhibitor of DNA methyltransferase (DNMT), targeting methylation-regulated gene expression. DM score was built by identifying 47 genes regulated by decitabine in human myeloma cell lines and the expression of which in primary MMCs of previously untreated patients is predictive for overall survival. A high DM score predicts patients' poor survival, and, of major interest, high sensitivity of primary MMCs or human myeloma cell lines to decitabine in vitro. Thus, DM score could be useful to design novel treatments with DMNT inhibitor in multiple myeloma and has highlighted 47 genes, the gene products of which could be important for multiple myeloma disease development. Mol Cancer Ther; 11(12); 2685–92. ©2012 AACR.
- Subjects :
- Cancer Research
MESH: Multiple Myeloma
Plasma cell
Bioinformatics
0302 clinical medicine
MESH: DNA Methylation
DNA Modification Methylases
Multiple myeloma
MESH: DNA Modification Methylases
Regulation of gene expression
0303 health sciences
MESH: Antimetabolites, Antineoplastic
DNA methylation inhibitors
MESH: Gene Expression Regulation, Neoplastic
Prognosis
MESH: Predictive Value of Tests
3. Good health
Gene Expression Regulation, Neoplastic
multiple myeloma
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
DNA methylation
Azacitidine
[SDV.IMM]Life Sciences [q-bio]/Immunology
medicine.drug
Antimetabolites, Antineoplastic
MESH: Cell Line, Tumor
[SDV.IMM] Life Sciences [q-bio]/Immunology
Decitabine
MESH: Azacitidine
Biology
DNA methyltransferase
MESH: Prognosis
03 medical and health sciences
MESH: Gene Expression Profiling
Predictive Value of Tests
Cell Line, Tumor
Biomarkers, Tumor
medicine
Humans
030304 developmental biology
MESH: Humans
Gene Expression Profiling
Cancer
DNA Methylation
medicine.disease
MESH: Tumor Markers, Biological
Cancer research
Bone marrow
Gene expression
Subjects
Details
- Language :
- English
- ISSN :
- 15357163 and 15388514
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer Therapeutics, Molecular Cancer Therapeutics, American Association for Cancer Research, 2012, 11 (12), pp.2685-92. ⟨10.1158/1535-7163.MCT-12-0721⟩
- Accession number :
- edsair.doi.dedup.....7eaf899fabfe217d64d162c888fa2f1b