Dataset Information


Differentiation of DLBCL induced by HDAC inhibitors is associated with sensitization to proteasome inhibition

ABSTRACT: Epigenetic modifying enzymes are commonly mutated in diffuse large B cell lymphoma (DLBCL), suggesting that epigenetic regulation is an important factor in DLBCL pathogenesis and a potential target for therapy. We developed resistant cell lines to histone deacetylase inhibitors (HDACi), one such epigenetic therapy, in order to define mechanisms of response and resistance. Strikingly, using gene expression and metabolic profiling, we found that development of HDACi resistance was associated with differentiation toward a plasmablast-like phenotype. Differentiation correlated with decreased B cell receptor signaling, increased ER stress and activation of the unfolded protein response, and increased sensitivity to proteasome inhibitors. Importantly, we found evidence of differentiation in lymphoma biopsies from patients treated with HDACi. Together, these data show, for the first time, that HDACi are differentiating agents in lymphoma and may be used to prime DLBCL for targeted therapy including proteasome inhibitors. Gene expression in DLBCL cells from tumor biopsies after 15 days panobinostat therapy

ORGANISM(S): Homo sapiens  

SUBMITTER: Koren Mann   Koren K Mann  Wilson H Miller 

PROVIDER: E-GEOD-59308 | ArrayExpress | 2016-08-01



Similar Datasets

2016-06-01 | E-GEOD-58421 | ArrayExpress
2011-02-15 | E-GEOD-27226 | ArrayExpress
2011-02-15 | GSE27226 | GEO
2014-04-09 | E-GEOD-56623 | ArrayExpress
2009-06-01 | GSE11902 | GEO
2009-06-01 | E-GEOD-11902 | ArrayExpress
| PRJNA137503 | ENA
2015-03-25 | E-MTAB-2926 | ArrayExpress
2015-03-25 | E-MTAB-2925 | ArrayExpress
2010-09-21 | GSE24236 | GEO