Pharmacological inhibition of chromatin co-regulatory factors represents a clinically validated strategy to modulate oncogenic signaling through selective attenuation of gene expression. Here, we demonstrate that CBP/EP300 bromodomain inhibition preferentially abrogates the viability of multiple myeloma cell lines. Phenotypic effects are preceded by the direct transcriptional suppression of the lymphocyte-specific transcription factor IRF4 and the subsequent down-regulation of the IRF4 transcriptional program. Ectopic expression of IRF4 antagonizes the phenotypic effects of CBP/EP300 bromodomain inhibition and prevents the suppression of the IRF4 target c-MYC. These findings suggest that CBP/EP300 bromodomain inhibition represents a viable therapeutic strategy for targeting multiple myeloma and other lymphoid malignancies dependent on the IRF4 network. Overall design: Through the use of CBP/EP300 bromodomain inhibitors (CBP/EP300i), we demonstrate that MYC expression in BETi-resistant cells is dependent on CBP/EP300 bromodomains and that treatment with CBP/EP300i restores phenotypic sensitivity.
Bromodomain inhibition of the transcriptional coactivators CBP/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma.
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View SamplesA new method for amplification and labeling of RNA is assessed that permits gene expression microarray analysis of formalin-fixed paraffin embedded tissue (i.e. FFPET) samples.
A novel method of amplification of FFPET-derived RNA enables accurate disease classification with microarrays.
Specimen part, Treatment
View SamplesWe performed DNA methylation (HELP array) and gene expression profiling in 69 samples of diffuse large B cell lymphoma (DLBCL). First, by gene expression, two molecular subtypes of DLBCL termed as "germinal center B cell-like" (GCB) and "activated B cell-like" (ABC) DLBCL were assigned to the 69 DLBCL cases. Then, the supervised analysis using HELP data revealed strikingly different DNA promoter methylation patterns in the two molecular DLBCL subtypes. These data provide epigenetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways.
DNA methylation signatures define molecular subtypes of diffuse large B-cell lymphoma.
Sex, Age, Specimen part
View SamplesWe used RNA-Seq to compare transcriptomes of chemical reprogramming competent worms versus worms not competent for chemical reprogramming. We also performed RNA-seq during a time course of chemical reprogramming. Overall design: Three replicates of each of two reprogramming non-competent strains and three replicates of each of two reprogramming competent strains were collected. For the time course, five time points were analyzed (1, 2, 4, 6, and 18 hours) in either DMSO or DMSO + U0126 in three genotypes (non-reprogramming competent worms, reprogramming competent, and wildtype worms).
Competence for chemical reprogramming of sexual fate correlates with an intersexual molecular signature in Caenorhabditis elegans.
Subject
View SamplesIn a supervised principal component analysis, histiocytes from TCHRBCL were most closely related to epithelioid cells from NLPHL, with both types of cells expressing genes related to proinflammatory and regulatory macrophage activity.
Macrophages in T cell/histiocyte rich large B cell lymphoma strongly express metal-binding proteins and show a bi-activated phenotype.
Specimen part
View SamplesTumor cells were microdissected from frozen sections of NLPHL and THRLBCL. RNA was amplified using the NUGEN WT-Ovation-One-direct-Kit. Samples were compared to tonsilar germinal center CD77 B cells.
Nodular lymphocyte predominant hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma--endpoints of a spectrum of one disease?
Specimen part
View SamplesHodgkin lymphoma is derived from germinal center / post-germinal center B cells.
Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma.
Sex, Age, Specimen part, Disease
View SamplesHodgkin lymphoma is derived from germinal center / post-germinal center B cells.
Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma.
Sex, Age, Specimen part, Disease
View SamplesHodgkin lymphoma is derived from germinal center / post-germinal center B cells.
Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma.
Specimen part
View SamplesExhaustion markers are expressed by T lymphocytes in Follicular Lymphoma (FL). Through these, TIM-3 has been recently identified as a poor pronostic factor when expressed by FL CD4+ T cells.
Impaired functional responses in follicular lymphoma CD8<sup>+</sup>TIM-3<sup>+</sup> T lymphocytes following TCR engagement.
Specimen part, Subject
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