Transcriptional plasticity promotes primary and acquired resistance to BET bromodomain inhibition

ABSTRACT: Following the discovery of BRD4 as a non-oncogene addiction target in acute myeloid leukemia (AML), BET inhibitors are being explored as promising therapeutic avenue in numerous cancers. While clinical trials have reported single-agent activity in advanced hematologic malignancies, mechanisms determining the response to BET inhibition remain poorly understood. To identify factors involved in primary and acquired BET resistance in leukemia, we performed a chromatin-focused shRNAmir screen in a sensitive MLL/AF9; NrasG12D‑driven AML model, and investigated dynamic transcriptional profiles in sensitive and resistant murine and human leukemias. Our screen reveals that suppression of the PRC2 complex, contrary to effects in other contexts, promotes BET resistance in AML. PRC2 suppression does n

ORGANISM(S): Mus musculus

SUBMITTER: Philipp Rathert 

PROVIDER: E-GEOD-63782 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress