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dc.contributor.authorKattih, Badder
dc.contributor.authorShirvani, Amir
dc.contributor.authorKlement, Piroska
dc.contributor.authorGarrido, Abel Martin
dc.contributor.authorGabdoulline, Razif
dc.contributor.authorLiebich, Alessandro
dc.contributor.authorBrandes, Maximilian
dc.contributor.authorChaturvedi, Anuhar
dc.contributor.authorSeeger, Timon
dc.contributor.authorThol, Felicitas
dc.contributor.authorGöhring, Gudrun
dc.contributor.authorSchlegelberger, Brigitte
dc.contributor.authorGeffers, Robert
dc.contributor.authorJohn, David
dc.contributor.authorBavendiek, Udo
dc.contributor.authorBauersachs, Johann
dc.contributor.authorGanser, Arnold
dc.contributor.authorHeineke, Joerg
dc.contributor.authorHeuser, Michael
dc.date.accessioned2020-10-14T14:32:40Z
dc.date.available2020-10-14T14:32:40Z
dc.date.issued2020-01-01
dc.identifier.citationLeukemia. 2020 Sep 18. doi: 10.1038/s41375-020-01043-x.en_US
dc.identifier.issn08876924
dc.identifier.pmid32948843
dc.identifier.doi10.1038/s41375-020-01043-x
dc.identifier.urihttp://hdl.handle.net/10033/622512
dc.description.abstractClonal hematopoiesis of indeterminate potential (CHIP) is linked to leukemia gene mutations and associates with an increased risk for coronary artery disease and poor prognosis in ischemic cardiomyopathy. Two recurrently mutated genes in CHIP and adult acute myeloid leukemia (AML) encode for isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2). Global expression of mutant IDH2 in transgenic mice-induced dilated cardiomyopathy and muscular dystrophy. In this retrospective observational study, we investigated whether mutant IDH1/2 predisposes to cardiovascular disease in AML patients. Among 363 AML patients, IDH1 and IDH2 mutations were detected in 26 (7.2%) and 39 patients (10.7%), respectively. Mutant IDH1 patients exhibited a significantly higher prevalence of coronary artery disease (26.1% vs. 6.4%, p = 0.002). Applying inverse probability-weighting analysis, patients with IDH1/2 mutations had a higher risk for a declining cardiac function during AML treatment compared to IDH1/2 wild type patients [left ventricular ejection fraction pretreatment compared to 10 months after diagnosis: 59.2% to 41.9% (p < 0.001) vs 58.5% to 55.4% (p = 0.27), respectively]. Mechanistically, RNA sequencing and immunostaining in hiPS-derived cardiomyocytes indicated that the oncometabolite R-2HG exacerbated doxorubicin mediated cardiotoxicity. Evaluation of IDH1/2 mutation status may therefore help identifying AML patients at risk for cardiovascular complications during cytotoxic treatment. Similar articlesen_US
dc.description.sponsorshipDeutsche Krebshilfeen_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleIDH1/2 mutations in acute myeloid leukemia patients and risk of coronary artery disease and cardiac dysfunction—a retrospective propensity score analysisen_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.identifier.eissn14765551
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalLeukemiaen_US
dc.identifier.eid2-s2.0-85091134192
dc.identifier.scopusidSCOPUS_ID:85091134192
refterms.dateFOA2020-10-14T14:32:40Z
dc.source.journaltitleLeukemia


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