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Here, we show that low\n                    <jats:italic>SUCNR1<\/jats:italic>\n                    represents a marker for reduced overall and progression-free survival in acute myeloid leukemia (AML) patients. Succinic acid, which displays Sucnr1-dependent and independent effects, promotes disease in mouse models of pre-leukemic myelopoiesis, AML and AML xenografts, expressing low\n                    <jats:italic>SUCNR1<\/jats:italic>\n                    . In vivo global or hematopoietic deletion of Sucnr1 induces expansion of hematopoietic stem and progenitor cells (HSPC) and hematopoiesis, whilst Sucnr1-tomato\n                    <jats:sup>+<\/jats:sup>\n                    HSPC display restricted engraftment potential. Mechanistically, activation of Sucnr1 counterbalances the stimulatory effect of intracellular succinate in HSPC and preserves HSPC transcriptional programs via control of S100a8\/S100a9. Blocking S100a9 with tasquinimod rescues the defects of Sucnr1 knock-out mice, and combined with a potent Sucnr1 agonist shows therapeutic value in AML mice. In AML xenografts, single-cell RNA-sequencing reanalyses confirm\n                    <jats:italic>SUCNR1<\/jats:italic>\n                    as a therapeutic vulnerability in patients. Together, Sucnr1 signaling restricts hematopoiesis at least partially through HSPC and via control of S100a8\/S100a9. Its dysregulation emerges as contributor to malignancy that opens therapeutic avenues for AML patients.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-68906-2","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T18:32:56Z","timestamp":1770316376000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-710X","authenticated-orcid":false,"given":"Vincent","family":"Cuminetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeline","family":"Boet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Heugel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4267-6012","authenticated-orcid":false,"given":"Joanna","family":"Konieczny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5741-7865","authenticated-orcid":false,"given":"Aurora","family":"Bernal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel J.","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Grimolizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3156-9908","authenticated-orcid":false,"given":"Nuria","family":"Vilaplana-Lopera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ferr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Villatoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deo P.","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8914-3400","authenticated-orcid":false,"given":"Carlos","family":"Torroja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagar","family":"Taman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-4143","authenticated-orcid":false,"given":"Ruth H.","family":"Paulssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9669-7479","authenticated-orcid":false,"given":"Thomas","family":"Vogl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4324-8706","authenticated-orcid":false,"given":"Caroline A.","family":"Heckman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Vik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5391-0441","authenticated-orcid":false,"given":"Giovanna","family":"Giovinazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-3590","authenticated-orcid":false,"given":"Nick","family":"van Gastel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-8575","authenticated-orcid":false,"given":"Paloma","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-1664","authenticated-orcid":false,"given":"F\u00e1tima","family":"S\u00e1nchez-Cabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6704-2032","authenticated-orcid":false,"given":"Jean-Emmanuel","family":"Sarry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5896-4238","authenticated-orcid":false,"given":"Lorena","family":"Arranz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"68906_CR1","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.stem.2018.04.003","volume":"22","author":"S Haas","year":"2018","unstructured":"Haas, S., Trumpp, A. & Milsom, M. 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