Targeting Acute Myeloid Leukemia Stem Cells through Perturbation of Mitochondrial Calcium.

ABSTRACT: Acute myeloid leukemia stem cells (LSCs) are uniquely reliant on oxidative phosphorylation (OXPHOS) for survival. Moreover, maintenance of OXPHOS is dependent on BCL-2, creating a therapeutic opportunity to target LSCs using the BCL-2 inhibitor venetoclax. Although venetoclax-based regimens have shown promising clinical activity, the emergence of drug resistance is prevalent. Thus, in the present study, we investigated how mitochondrial properties may influence venetoclax responsiveness. Our data show that utilization of mitochondrial calcium is fundamentally different between drug-responsive and nonresponsive LSCs. By comparison, venetoclax-resistant LSCs demonstrate an active metabolic (i.e., OXPHOS) status with relatively high levels of calcium. Consequently, we tested genetic and pharm

SUBMITTER: Sheth AI 

PROVIDER: S-EPMC11452272 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature