High Metabolic Dependence on Oxidative Phosphorylation Drives Sensitivity to Metformin Treatment in MLL/AF9 Acute Myeloid Leukemia.
Longlong LiuPradeep Kumar PatnanaXiaoqing XieDaria FrankSubbaiah Chary NimmagaddaAnnegret RosemannMarie LiebmannLuisa KlotzBertram OpalkaCyrus KhandanpourPublished in: Cancers (2022)
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 MLL/AF9 have upregulated mitochondrial activity and mainly depend on OXPHOS for energy production. Furthermore, we show that metformin repressed the proliferation of MLL/AF9 AML cells by inhibiting mitochondrial respiration. Together, this study demonstrates that AML cells with an MLL/AF9 genotype have a high dependency on OXPHOS and could be therapeutically targeted by metformin.
Keyphrases
- acute myeloid leukemia
- induced apoptosis
- allogeneic hematopoietic stem cell transplantation
- stem cells
- cell cycle arrest
- atrial fibrillation
- signaling pathway
- oxidative stress
- endoplasmic reticulum stress
- gene expression
- single cell
- end stage renal disease
- cell proliferation
- dna methylation
- ejection fraction
- acute lymphoblastic leukemia
- protein kinase
- pi k akt
- radiation therapy
- chronic kidney disease
- copy number
- peritoneal dialysis
- young adults