Venetoclax promotes acute myeloid leukemia cells apoptosis by decreasing ac4C modification and mRNA expression of IMP3 through downregulating NAT10.

Venetoclax, a common treatment for acute myeloid leukemia (AML), exhibits unclear mechanisms. This study investigates whether venetoclax regulates AML apoptosis via NAT10, which is upregulated in AML and linked to poor prognosis. HL60 and KG-1 cell lines were treated with varying venetoclax concentrations, and cell viability, apoptosis, and protein levels of apoptosis-related markers were assessed using CCK-8, flow cytometry, and Western blotting. Molecular docking confirmed the interaction between venetoclax and NAT10. Venetoclax inhibited cell viability and promoted apoptosis in a dose-dependent manner, effects reversed by NAT10 overexpression. Mechanistically, NAT10 knockdown reduced IMP3 mRNA expression by decreasing its ac4C modification, suppressing cell viability and promoting apoptosis, effects restored by IMP3 overexpression. Thus, venetoclax downregulates NAT10 to inhibit IMP3 expression and enhance AML cell apoptosis, providing new insights for its clinical use.