Targeting METTL3 mitigates venetoclax resistance via proteasome-mediated modulation of MCL1 in acute myeloid leukemia.

ABSTRACT: Venetoclax, a selective BCL2 inhibitor, is extensively utilized in clinical settings for the treatment of acute myeloid leukemia (AML). However, its efficacy is often compromised by the development of drug resistance. Hence, identification of potential venetoclax combination treatment strategies is imperative to overcome this acquired resistance. In this study, we discovered that inhibition of METTL3 can synergistically enhance the anti-leukemic efficacy of venetoclax, and is capable of overcoming venetoclax resistance in in vivo experiments and various venetoclax resistance models. Mechanistic study revealed that STM2457 augmented venetoclax activity by downregulating MCL1 and MYC, thereby increasing apoptosis in leukemia cells induced by venetoclax. Further investigation demonstrated tha

SUBMITTER: Jiao CQ 

PROVIDER: S-EPMC11962166 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature