Antileukemic effect of venetoclax and hypomethylating agents via caspase-3/GSDME-mediated pyroptosis.

ABSTRACT:

Background

The identifying of B-cell lymphoma 2 (Bcl-2) as a therapeutic target has led to a paradigm shift in acute myeloid leukemia (AML) treatment. Pyroptosis is a novel antitumor therapeutic mechanism due to its cytotoxic and immunogenic effects. The combination of venetoclax and hypomethylating agents (HMAs) has been shown to lead to durable responses and significantly improve prognosis in patients with AML. However, our understanding of the mechanisms underlying this combinatorial activity is evolving.

Methods

We investigated whether the Bcl-2 inhibitor venetoclax induces AML cell pyroptosis and identified pyroptosis effector proteins. Via using western blotting, immunoprecipitation, RNA interference, CCK8 assays, and LDH assays, we explored the mechanism underlying th

SUBMITTER: Ye F 

PROVIDER: S-EPMC10486003 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature