Role of Lysophospholipid Metabolism in Chronic Myelogenous Leukemia Stem Cells
Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
Academic Editor: Masahiro Kizaki
Received: 10 May 2021 / Revised: 5 July 2021 / Accepted: 7 July 2021 / Published: 8 July 2021
In this review, I discuss our recent finding that lysophospholipid metabolism is essential for the maintenance of chronic myelogenous leukemia (CML) stem cells. Lysophospholipids have only one fatty acid chain and so are more hydrophilic than phospholipids, allowing them to act as lipid second messengers. We demonstrated that the stem cell quiescence and TKI resistance displayed by CML stem cells in vivo are sustained by the Gdpd3 enzyme involved in lysophospholipid metabolism. At the mechanistic level, Gdpd3 function allows lysophospholipid metabolism to suppress the AKT/mTORC1-mediated cell growth pathway while activating the stemness factors FOXO and β-catenin. Our results thus link lysophospholipid metabolism to CML stemness, and may thereby open up new therapeutic avenues to overcome CML relapse post-TKI therapy.