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In this study, we investigated the role of GPR44, a G-protein coupled receptor of arachidonic acid-derived prostaglandin D\n                    <jats:sub>2<\/jats:sub>\n                    (PGD\n                    <jats:sub>2<\/jats:sub>\n                    ) and its cyclopentenone prostaglandins (CyPGs) metabolites, \u0394\n                    <jats:sup>12<\/jats:sup>\n                    -PGJ\n                    <jats:sub>2<\/jats:sub>\n                    and 15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    , in regulating selenium metabolism and selenoprotein expression in AML LICs. Transplantation of\n                    <jats:italic>Gpr44<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    LICs into donor mice led to aggressive leukemogenesis. Transcriptomic and proteomic analyses revealed that GPR44 deletion significantly altered the selenoproteome, with downregulation of Txnrd1, Txnrd3, Selenop, and Gpx2, while upregulating Gpx3, Gpx4, Selenoo, and Msrb1. These findings suggest that GPR44 influences redox homeostasis and leukemic cell survival by modulating selenium utilization. Notably, increased expression of eIF4a3 in\n                    <jats:italic>Gpr44<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    LICs suggested a potential mechanism for selective selenoprotein repression through SECIS-binding protein 2 (SBP2) inhibition. Additionally, upregulation of SBP2 and selenophosphate synthetase 2 (SPS2) indicated an adaptive response to maintain selenium incorporation. Given the role of selenium in redox balance, metabolism, and immune function, targeting selenium metabolism in GPR44-expressing AML may offer a novel therapeutic approach. Our findings reveal a previously unrecognized link between GPR44 signaling, selenium metabolism, and leukemia progression, warranting further studies to explore selenoprotein-targeting strategies for AML treatment.\n                  <\/jats:p>","DOI":"10.1007\/s12011-025-04724-9","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:23:39Z","timestamp":1750983819000},"page":"1001-1007","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GPR44-Dependent Regulation of the Selenoproteome by eIF4a3 in Murine Acute Myeloid Leukemia-Initiating Stem Cells"],"prefix":"10.1007","volume":"204","author":[{"given":"Deborpita","family":"Sarkar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenghua","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert F.","family":"Paulson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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