Abstract 4516: Evaluating the chromatin state as a predictive biomarker for BET inhibitor sensitivity in hematological malignancies

Abstract

Abstract The BET (bromodomain extra-terminal) family of proteins are a group of epigenetic regulators that control gene transcription by reading acetylated lysines on histone tails and recruiting transcription complexes. The various BET inhibitors developed show strong anti-tumor effects against a broad range of hematologic malignancies. The BET inhibitor JQ1 shows strong anti-proliferative activity in sub-sets of multiple myeloma (MM), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and lymphoma cell line models. At present, however, predictive biomarkers of BET inhibitor sensitivity have not been identified. We hypothesize that the chromatin state characterized by various histone post-translational modifications (acetylation, methylation, etc.), can drive sensitivity to BET inhibition. By examining basal expression of epigenetic marks in panels of sensitive and resistant heme cell line models and further validating these histone modification trends in primary AML and multiple myeloma cultures, we may be able to identify predictive biomarkers of BET inhibitor sensitivity in hematological malignancies. Citation Format: Joseph Castillo, Ryan Raisner, Karen Gascoigne, Gary Dos Santos, Emer Clarke, Alex Huang, Mark Lackner, Zineb Mounir. Evaluating the chromatin state as a predictive biomarker for BET inhibitor sensitivity in hematological malignancies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4516.