Project description:Bortezomib therapy has been proven successful for the treatment of relapsed and/or refractory multiple myeloma (MM). However, both intrinsic and acquired resistance has already been observed. In this study, we explored the relationship between CD9 expression and bortezomib sensitivity in MM Both intrinsic and acquired resistance has already been observed. In this study, we explored the relationship between CD9 expression and bortezomib sensitivity in MM. We found that down-regulation of CD9 by methylation decreased bortezomib sensitivity in multiple myeloma. A six chip study using total RNA recovered from three separate wild-type cultures of U266 cells and three separate cultures of U266 with CD9 overexpression. Each chip measures the expression level of 45,033 genes from Homo sapiens with fourteen 60-mer probe pairs (PM/MM) per gene, with three-fold technical redundancy.
Project description:EFNB2 is a cell transmembrane protein required for the survival of multiple myeloma cells. Specifically, we have previously shown that EFNB2 reverse signaling is required for myeloma proliferation and survival. Overexpressing EFNB2 increases myeloma survival, proliferation, and resistance to treatment. This effect is mediated partially through STAT5, but other mediators are likely invovled. To determine if other mediators and pathways might be involved, we performed RNA-seq on myeloma cells overepxressing EFNB2.
Project description:Purpose: We examined how transcriptional state changes relate to clonal selection as BRAF inhibitor resistance develops in BRAF-mutated myeloma. Methods: To this end we generated three single-cell clones from U266, a BRAFK601N -mutated myeloma cell line and DP6- a BRAFV600E myeloma cell line. All three U266 and DP6 clones were subjected to long-term dabrafenib treatment at their established IC50 doses (U266: 10uM, DP6 1nM). Bulk RNA-seq was performed before treatment, day 7, day 14, day 42 and at time of resistance. Results: Transcriptional adaptation after seven days was homogeneous for all clones, but was different across both cell lines. Oxidative phosphorylation (OxPhos) emerged as the most consistently enriched signaling pathway in persistent cells from both cell lines as compared to baseline. Conclusions: BRAF inhibition in BRAF-mutated myeloma cells leads to transcriptional reprogramming with induction of OxPhos-related genes within a brief period of time.
Project description:To identify epigenetically silenced genes in multiple myeloma (MM) cell lines and to determine the effects of 5-aza-2-deoxycytidine and trichostatin A on gene expression. We treated 3 multiple myeloma cell lines (MM1, NCI-H929, U266) with 5-aza-2-deoxycytidine and/or trichostatin A.
Project description:We used microarrays to examine changes in gene expression in multiple myeloma cell lines following treatment with arsenic trioxide and darinaparsin Experiment Overall Design: Four multiple myeloma cell lines (U266, MM.1s, KMS11, 8226/S) were treated with either arsenic trioxide (ATO) for 6, 24, or 48 hours or darinaparsin (DAR) for 6 or 24 hours; RNA was extracted from treated and control cells for microarray analysis
Project description:RNA-seq experiments was conducted to analyze changes in related signaling pathways and gene expression in multiple myeloma cells when G6PD was overexpression.