Fatty Acid Metabolism, Bone Marrow Adipocytes, and AML

Frontiers in Oncology

Marina Konopleva²  Michael Andreeff³  Yoko Tabe³ 

[1] Department of Laboratory Medicine, Juntendo University, Tokyo, Japan;Section of Leukemia Biology Research, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;

关键词: fatty acid metabolism;    fatty acid oxidation;    bone marrow microenvironment;    adipocyte;    therapy resistance;   

DOI  :  10.3389/fonc.2020.00155

来源: DOAJ

【 摘 要 】

Acute myeloid leukemia (AML) cells modulate their metabolic state continuously as a result of bone marrow (BM) microenvironment stimuli and/or nutrient availability. Adipocytes are prevalent in the BM stroma and increase in number with age. AML in elderly patients induces remodeling and lipolysis of BM adipocytes, which may promote AML cell survival through metabolic activation of fatty acid oxidation (FAO). FAO reactions generate acetyl-CoA from fatty acids under aerobic conditions and, under certain conditions, it can cause uncoupling of mitochondrial oxidative phosphorylation. Recent experimental evidence indicates that FAO is associated with quiescence and drug-resistance in leukemia stem cells. In this review, we highlight recent progress in our understanding of fatty acid metabolism in AML cells in the adipocyte-rich BM microenvironment, and discuss the therapeutic potential of combinatorial regimens with various FAO inhibitors, which target metabolic vulnerabilities of BM-resident, chemoresistant leukemia cells.

【 授权许可】

Unknown