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Two recurrently mutated genes in CHIP and adult acute myeloid leukemia (AML) encode for isocitrate dehydrogenases 1 and 2 (<jats:italic>IDH1<\/jats:italic> and <jats:italic>IDH2<\/jats:italic>). Global expression of mutant <jats:italic>IDH2<\/jats:italic> in transgenic mice-induced dilated cardiomyopathy and muscular dystrophy. In this retrospective observational study, we investigated whether mutant <jats:italic>IDH1\/2<\/jats:italic> predisposes to cardiovascular disease in AML patients. Among 363 AML patients, <jats:italic>IDH1<\/jats:italic> and <jats:italic>IDH2<\/jats:italic> mutations were detected in 26 (7.2%) and 39 patients (10.7%), respectively. Mutant <jats:italic>IDH1<\/jats:italic> patients exhibited a significantly higher prevalence of coronary artery disease (26.1% vs. 6.4%, <jats:italic>p<\/jats:italic>\u2009=\u20090.002). Applying inverse probability-weighting analysis, patients with <jats:italic>IDH1\/2<\/jats:italic> mutations had a higher risk for a declining cardiac function during AML treatment compared to <jats:italic>IDH1\/2<\/jats:italic> wild type patients [left ventricular ejection fraction pretreatment compared to 10 months after diagnosis: 59.2% to 41.9% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) vs 58.5% to 55.4% (<jats:italic>p<\/jats:italic>\u2009=\u20090.27), respectively]. Mechanistically, RNA sequencing and immunostaining in hiPS-derived cardiomyocytes indicated that the oncometabolite R-2HG exacerbated doxorubicin mediated cardiotoxicity. Evaluation of <jats:italic>IDH1\/2<\/jats:italic> mutation status may therefore help identifying AML patients at risk for cardiovascular complications during cytotoxic treatment.<\/jats:p>","DOI":"10.1038\/s41375-020-01043-x","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T11:10:05Z","timestamp":1600427405000},"page":"1301-1316","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["IDH1\/2 mutations in acute myeloid leukemia patients and risk of coronary artery disease and cardiac dysfunction\u2014a retrospective propensity score analysis"],"prefix":"10.1038","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1324-5536","authenticated-orcid":false,"given":"Badder","family":"Kattih","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Shirvani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piroska","family":"Klement","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel Martin","family":"Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razif","family":"Gabdoulline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Liebich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Brandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-3010","authenticated-orcid":false,"given":"Anuhar","family":"Chaturvedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timon","family":"Seeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"Thol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"G\u00f6hring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Schlegelberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4409-016X","authenticated-orcid":false,"given":"Robert","family":"Geffers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Bavendiek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-117X","authenticated-orcid":false,"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Ganser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1541-3030","authenticated-orcid":false,"given":"Joerg","family":"Heineke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-9044","authenticated-orcid":false,"given":"Michael","family":"Heuser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"1043_CR1","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","volume":"374","author":"E Papaemmanuil","year":"2016","unstructured":"Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. 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