Synergistic activity of BET protein antagonist-based combinations in Mantle Cell Lymphoma cells sensitive or resistant to ibrutinib

ABSTRACT: To determine the global transcriptome changes in mantle cell lymphoma cells following treatment with the BET bromodomain antagonist, JQ1 Mantle Cell Lymphoma (MCL) cells exhibit increased B cell receptor and NFkB activities. The BET protein BRD4 is essential for the transcriptional activity of NFkB. Here, we demonstrate that treatment with the BET protein bromodomain antagonist (BA) JQ1 attenuates MYC and CDK4/6, inhibits the nuclear RelA levels and the expression of NFκB target genes including Bruton’s Tyrosine Kinase (BTK) in MCL cells. While lowering the levels of the anti-apoptotic BCL2 family proteins, BA treatment induces the pro-apoptotic protein BIM and exerts dose-dependent lethality against cultured and primary MCL cells. Co-treatment with BA and the BTK inhibitor ibrutinib sy

ORGANISM(S): Homo sapiens

SUBMITTER: Kapil Bhalla 

PROVIDER: E-GEOD-70651 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress