High Metabolic Dependence on Oxidative Phosphorylation Drives Sensitivity to Metformin Treatment in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a group of hematological cancers with metabolic heterogeneity. Oxidative phosphorylation (OXPHOS) has been reported to play an important role in the function of leukemic stem cells and chemotherapy-resistant cells and are associated with inferior prognosis in AML patients. However, the relationship between metabolic phenotype and genetic mutations are yet to be explored. In the present study, we demonstrate that AML cell lines have high metabolic heterogeneity, and AML cells with have upregulated mitochondrial activity and mainly depend on OXPHOS for energy production. Furthermore, we show that metformin repressed the proliferation of AML cells by inhibiting mitochondrial respiration. Together, this study demonstrates that AML cells with an genotype have a high dependency on OXPHOS and could be therapeutically targeted by metformin.