Mitochondrial metabolism as a target for acute myeloid leukemia treatment.
Svetlana B PaninaJingqi PeiNatalia V KirienkoPublished in: Cancer & metabolism (2021)
Acute myeloid leukemias (AML) are a group of aggressive hematologic malignancies resulting from acquired genetic mutations in hematopoietic stem cells that affect patients of all ages. Despite decades of research, standard chemotherapy still remains ineffective for some AML subtypes and is often inappropriate for older patients or those with comorbidities. Recently, a number of studies have identified unique mitochondrial alterations that lead to metabolic vulnerabilities in AML cells that may present viable treatment targets. These include mtDNA, dependency on oxidative phosphorylation, mitochondrial metabolism, and pro-survival signaling, as well as reactive oxygen species generation and mitochondrial dynamics. Moreover, some mitochondria-targeting chemotherapeutics and their combinations with other compounds have been FDA-approved for AML treatment. Here, we review recent studies that illuminate the effects of drugs and synergistic drug combinations that target diverse biomolecules and metabolic pathways related to mitochondria and their promise in experimental studies, clinical trials, and existing chemotherapeutic regimens.
Keyphrases
- acute myeloid leukemia
- stem cells
- oxidative stress
- reactive oxygen species
- allogeneic hematopoietic stem cell transplantation
- newly diagnosed
- ejection fraction
- gene expression
- radiation therapy
- immune response
- emergency department
- copy number
- acute lymphoblastic leukemia
- randomized controlled trial
- drug induced
- dna methylation
- intensive care unit
- dendritic cells
- prognostic factors
- hepatitis b virus
- drug delivery
- rectal cancer
- mesenchymal stem cells
- extracorporeal membrane oxygenation
- adverse drug
- pi k akt
- mechanical ventilation