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In this study, we reveal a synthetic lethal interaction between\n                    <jats:italic>BCOR<\/jats:italic>\n                    and dihydroorotate dehydrogenase (DHODH). We demonstrate that\n                    <jats:italic>BCOR<\/jats:italic>\n                    -deficient cells have a heightened sensitivity to DHODH inhibitors such as brequinar and leflunomide, that are already in clinical use. We confirm that DHODH inhibition selectively induces cell death in BCOR-mutant cells in multiple cellular models, in malignant and non-malignant cells, through chemical and genetic manipulation. Interestingly, we find that the dependency on DHODH does not stem from its role in\n                    <jats:italic>de novo<\/jats:italic>\n                    pyrimidine biosynthesis disruption. Rather, DHODH\u2019s role in the electron transport chain, essential for mitigating reactive oxygen species, may be the physiological vulnerability that pushes BCOR-mutant cells toward cell death when DHODH is inhibited. DHODH inhibitors could be repurposed as targeted therapies for BCOR-mutant tumors, offering a promising strategy for precision medicine in AML and other cancers.\n                  <\/jats:p>","DOI":"10.1007\/s00277-026-06773-z","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T01:45:36Z","timestamp":1768787136000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["BCOR mutations define a therapeutic vulnerability to DHODH Inhibition in acute myeloid leukemia"],"prefix":"10.1007","volume":"105","author":[{"given":"Florian","family":"Robert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherif","family":"Badja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya","family":"Boushaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Degasperi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasin","family":"Memari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Momen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros I.","family":"Roumeliotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuza","family":"Kozik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Gozdecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti","family":"Choudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Vassiliou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene CC","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Nik-Zainal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"issue":"12","key":"6773_CR1","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1056\/NEJMra1406184","volume":"373","author":"H D\u00f6hner","year":"2015","unstructured":"D\u00f6hner H, Weisdorf DJ, Bloomfield CD (2015) Acute myeloid leukemia. 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