Redox metabolism maintains the leukemogenic capacity and drug resistance of AML cells.

ABSTRACT: Rewiring of redox metabolism has a profound impact on tumor development, but how the cellular heterogeneity of redox balance affects leukemogenesis remains unknown. To precisely characterize the dynamic change in redox metabolism in vivo, we developed a bright genetically encoded biosensor for H₂O₂ (named HyPerion) and tracked the redox state of leukemic cells in situ in a transgenic sensor mouse. A H₂O₂-low (HyPerion-low) subset of acute myeloid leukemia (AML) cells was enriched with leukemia-initiating cells, which were endowed with high colony-forming ability, potent drug resistance, endosteal rather than vascular localization, and short survival. Significantly high expression of malic enzymes, including ME1/3, accounted for nicotinamide adeni

SUBMITTER: Huang D 

PROVIDER: S-EPMC10068762 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature