Targeting NRF2 uncovered an intrinsic susceptibility of acute myeloid leukemia cells to ferroptosis.

ABSTRACT: Drug resistance and poor treatment response are major obstacles to the effective treatment of acute myeloid leukemia (AML). A deeper understanding of the mechanisms regulating drug resistance and response genes in AML is therefore urgently needed. Our previous research has highlighted the important role of nuclear factor E2-related factor 2 (NRF2) in AML, where it plays a critical role in detoxifying reactive oxygen species and influencing sensitivity to chemotherapy. In this study, we identify a core set of direct NRF2 targets that are involved in ferroptosis, a novel form of cell death. Of particular interest, we find that glutathione peroxidase 4 (GPX4) is a key ferroptosis gene that is consistently upregulated in AML, and high expression of GPX4 is associated with poor prognosis for AM

SUBMITTER: Liu X 

PROVIDER: S-EPMC10189915 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature