PPARγ-induced upregulation of fatty acid metabolism confers resistance to venetoclax and decitabine therapy in AML.

ABSTRACT: The combination of the B-cell lymphoma 2 (BCL2) inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC; VEN/DEC) constitutes a primary therapeutic strategy for treating older adults with acute myeloid leukemia (AML). However, a notable subset of patients exhibits resistance to VEN/DEC, demonstrating either no disease response or relapse after initial remission. This study aimed to elucidate the molecular mechanisms underlying this resistance through analyses of gene expression and DNA methylation profiles. We conducted comprehensive RNA sequencing analysis and DNA methylation profiling on AML samples from 35 patients undergoing VEN/DEC therapy. The RNA sequencing analysis revealed that several genes related to fatty acid metabolism were significantly upregulated in leukem

SUBMITTER: Yamatani K 

PROVIDER: S-EPMC12318265 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature