Transcriptional and phenotypic heterogeneity underpinning venetoclax resistance in AML.

ABSTRACT: The venetoclax BCL2 inhibitor in combination with hypomethylating agents represents a cornerstone of induction therapy for older AML patients, unfit for intensive chemotherapy. Like other targeted therapies, venetoclax-based therapies suffer from innate and acquired resistance. While several mechanisms of resistance have been identified, the heterogeneity of resistance mechanism across patient populations is poorly understood. Here we utilized integrative analysis of transcriptomic and ex-vivo drug response data in AML patients to identify four transcriptionally distinct VEN resistant clusters (VR_C1-4), with distinct phenotypic, genetic and drug response patterns. VR_C1 was characterized by enrichment for differentiated monocytic- and cDC-like blasts, transcriptional activation of

SUBMITTER: Mohanty V 

PROVIDER: S-EPMC10862759 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature