Fatty Acid Metabolism, Bone Marrow Adipocytes, and AML

Frontiers in Oncology
Yoko TabeMichael Andreeff

Abstract

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.

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Citations

Jun 4, 2020·International Journal of Molecular Sciences·Cristina PanuzzoDaniela Cilloni
Sep 3, 2020·International Journal of Molecular Sciences·Laura AnselmiAndrea Pession
Oct 20, 2020·Frontiers in Cell and Developmental Biology·Drenka TrivanovićAleksandra Jauković
Dec 19, 2020·Signal Transduction and Targeted Therapy·Jenna L CarterYubin Ge
Mar 20, 2021·Molecular Therapy Oncolytics·Chengsheng DingZhiming Jin
Jun 22, 2021·Frontiers in Oncology·Fei HanXi Jiang
Jul 25, 2021·Leukemia·Sarah TettamantiMarta Serafini

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