Multiple myeloma cell lines expression profile of OTX015-treated cells compared to DMSO controls
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ABSTRACT:
PROVIDER: PRJNA436970 | ENA |
REPOSITORIES: ENA
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Project description:Several studies demonstrate that the bromodomain inhibitor OTX015 has preclinical antitumor activity in a variety of solid tumors and hematologic cancers. However, translation of these data to molecules suitable for clinical development has not yet to be accomplished in multiple myeloma (MM). Here, we identified genes and biologic processes that underpin the antimyeloma activity of OTX015 with global transcriptomics. OTX015 exerted strong antiproliferative effect and induced cell cycle arrest in vitro. Gene expression profiling showed that OTX015 targeted NF-κB, EGFR, cell cycle regulation, cancer proliferation signaling pathway. Gene expression signatures associated with different sensitivity to OTX015 were also identified. The data also showed that oral administration of OTX015 displayed significant antitumor activity in mice model of disseminated human myeloma. In addition, our study provided the first evidence and rationale that OTX015 could promoted osteoblast differentiation of mesenchymal stem cells (MSCs) and inhibited osteoclast formation and resorption in vivo experiments. Herein we expanded the mechanistic understanding of BET inhibitors OTX015 in MM. Our preclinical studies provided a strong rationale for extending the clinical testing of the novel antimyeloma agent OTX015 and revealed insights into biologic pathways required for myeloma cell proliferation.
2019-03-08 | GSE111422 | GEO
Project description:Gene signature determination of the effect of a new bromodomain inhibitor among a representative set of leukemic cell lines OTX015 vs. DMSO and JQ1 vs. DMSO
2015-06-25 | E-GEOD-70263 | biostudies-arrayexpress
Project description:We used a total of 10 human multiple myeloma cell lines for the study (KMS-20, KMS-28BM, MOLP-8, RPMI-8226, U-266, KMS-11, KMS-12-PE, KMS-34, LP-1 and NCI-H929). Cells (2 x 105 per well) were seeded into six-well culture plates in the appropriate culture media 24 h before treatment. Five replicate wells were then exposed to 2 uM of E7438 or control DMSO for 3 days. Cells were collected and RNA was extracted using RNeasy kit (Qiagen) according to the manufacturer’s instructions. For each sample, 250ng of total RNA was amplified using the Affymetrix GeneChip WT PLUS Reagent Kit according to the protocol described in User Manual Target Preparation for GeneChip Whole Transcript (WT) Expression Arrays (P/N 703174 Rev. 2). An Affymetrix Human Gene 2.1 ST 96-array plate was hybridized with 3µg of fragmented and labeled ss cDNA, washed, stained, and scanned according to the protocol described in User Manual GeneTitan®Instrument User Guide for Expression Arrays Plates (P/N 702933 Rev.1) and Affymetrix® GeneChip® Command Console™ User’s Guide (P/N 702569 Rev.9) using the Affymetrix GeneTitan instrument.
2016-01-11 | E-MTAB-3540 | biostudies-arrayexpress
Project description:Multiple myeloma is a relatively common B-cell malignancy that is currently incurable. Certain recurrent genetic abnormalities characteristics of different genetic subtypes have been described. Hyperdiploid myeloma characterized by recurrent trisomies is the most common genetic subtypes. However little is know about it's biology. Another common genetic abnormality is chromosome 13 deletion which is also associated with inferior prognosis. This abnormality is already present at the pre-malignant MGUS stage and is clonally selected with disease progression. Although it is biologically and clinically important the molecular consequence of chromosome 13 deletion is unknown. Experiment Overall Design: Hyperdiploid myeloma was identified using FISH. The gene expression profile of hyperdiploid MM is compared to that of non-hyperdiploid myeloma to identify differentially expressed genes. Molecular heterogeneity within H-MM is analyzed using unsupervised techniques. The distinctive subgroups identified are also tested in MGUS/SMM and NH-MM. The clinical relevance of these subtypes of hyperdiploid myeloma is then analyzed by correlating with relevant clinical information. Chromosome 13 deleted and undeleted MM are identified by FISH and their gene expression profile compared to identify molecular signature.
2008-06-15 | E-GEOD-6477 | biostudies-arrayexpress
Project description:miRNA profiling in multiple myeloma - microRNAs represent a class of noncoding regulators of gene expression implicated in several biological and pathophysiological processes, including cancer. We investigate here their role in multiple myeloma using miChip-arrays interrogating 559 miRNAs in 92 purified myeloma-, MGUS-, normal plasma cell- and myeloma cell line samples. Impact on gene expression is assessed by Affymetrix U133 2.0 DNA-microarrays in 741 samples including two cohorts of 332 and 345 myeloma patients; chromosomal aberrations are assessed by iFISH, survival for 247 and 345 patients undergoing up-front high-dose therapy and autologous stem cell transplantation. Compared to normal plasma cells, 67/559 (12%) miRNAs are differentially expressed with fold changes of 4.6 to -3.1 in myeloma-, 20 (3.6%) in MGUS-samples, and three (0.5%) between MGUS- and myeloma-samples. Expression of miRNAs is associated with biological and pathophysiological parameters, i.e. proliferation, chromosomal aberrations, e.g. t(4;14), tumor mass, and gene expression-based high-risk scores. This holds true for target-gene signatures of regulated mRNAs. miRNA-expression confers prognostic significance for event-free (72/559) and overall survival (69/559), as do respective target-gene signatures. In conclusion, the miRNome of myeloma confers a pattern of small changes of individual miRNAs compared to normal plasma cells impacting on gene expression, biological functions, and survival.
2014-01-09 | E-MTAB-1363 | biostudies-arrayexpress
Project description:We found that a small molecule inhibitor of PRMT4 inhibited cell growth of a subset of multiple myeloma cell lines. To identify biomarkers that predict the sensitivity of myeloma cells to PRMT4 inhibition, we performed transcriptomic analysis of multiple myeloma cell lines.
2018-02-06 | GSE110180 | GEO
Project description:We performed genome-wide miRNA expression profiling (MEP) of a panel of four human Myeloma cell lines treated with 5'azacytidine compared to control (DMSO treatment), with the objective of unmasking miRNAs silenced by DNA hypermethylation.
2015-08-31 | GSE53850 | GEO
Project description:Evaluation of anti-myeloma effects of inhibition of PRMT5, involved in arginine methylation. Three human multiple myeloma cell lines were treated with the PRMT5 inhibitor EPZ015938. Transcriptional profiles were compared to untreated controls.
2022-03-11 | E-MTAB-11489 | biostudies-arrayexpress
Project description:Transcriptional profiling of the human pancreatic cancer cell line SUIT-2 that were infected with a GFP encoding adenoviral construct based on Human Adenovirus 5 and treated with epigenetic modifiers I-bet-762, NEO27034 or OTX015 compared to uninfected and untreated cells. Cells were infected with 1pfu AdWTGFP in serum free media for 2 hours. Cells were then washed and cultured in media containing 2% FBS for 10 hours. Cells were then treated with I-bet-762, NEO27034, OTX015 or DMSO in media containing 2% FBS for 12 hours. Infected GFP+ cells were isolated by FACS. GFP+ and control cells were processed for RNA-seq.
2024-02-14 | E-MTAB-13108 | biostudies-arrayexpress