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However, AML\u2010specific molecular mechanisms that regulate mitochondrial dynamics remain elusive. Through the metabolite screening comparing CD34<jats:sup>+<\/jats:sup> AML cells and healthy hematopoietic stem\/progenitor cells, we identified enhanced lysophosphatidic acid (LPA) synthesis activity in AML. LPA is synthesized from glycerol\u20103\u2010phosphate by glycerol\u20103\u2010phosphate acyltransferases (GPATs), rate\u2010limiting enzymes of the LPA synthesis pathway. Among the four isozymes of GPATs, glycerol\u20103\u2010phosphate acyltransferases, mitochondrial (GPAM) was highly expressed in AML cells, and the inhibition of LPA synthesis by silencing GPAM or FSG67 (a GPAM\u2010inhibitor) significantly impaired AML propagation through the induction of mitochondrial fission, resulting in the suppression of oxidative phosphorylation and the elevation of reactive oxygen species. Notably, inhibition of this metabolic synthesis pathway by FSG67 administration did not affect normal human hematopoiesis in vivo. Therefore, the GPAM\u2010mediated LPA synthesis pathway from G3P represents a critical metabolic mechanism that specifically regulates mitochondrial dynamics in human AML, and GPAM is a promising potential therapeutic target.<\/jats:p>","DOI":"10.1111\/cas.15835","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:19:18Z","timestamp":1684369158000},"page":"3247-3258","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>GPAM<\/scp> mediated lysophosphatidic acid synthesis regulates mitochondrial dynamics in acute myeloid leukemia"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9354-4661","authenticated-orcid":false,"given":"Hidetoshi","family":"Irifune","sequence":"first","affiliation":[{"name":"Department of Medicine and Biosystemic Sciences Kyushu University Graduate School of Medicine  Fukuoka 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