IDH1/2 mutations in acute myeloid leukemia patients and risk of coronary artery disease and cardiac dysfunction—a retrospective propensity score analysis

  1. Kattih, Badder ORCID logo
  2. Shirvani, Amir
  3. Klement, Piroska
  4. Garrido, Abel Martin
  5. Gabdoulline, Razif
  6. Liebich, Alessandro
  7. Brandes, Maximilian
  8. Chaturvedi, Anuhar ORCID logo
  9. Seeger, Timon
  10. Thol, Felicitas
  11. Göhring, Gudrun
  12. Schlegelberger, Brigitte
  13. Geffers, Robert ORCID logo
  14. John, David
  15. Bavendiek, Udo
  16. Bauersachs, Johann ORCID logo
  17. Ganser, Arnold
  18. Heineke, Joerg ORCID logo
  19. Heuser, Michael ORCID logo

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1000 Titel
  • IDH1/2 mutations in acute myeloid leukemia patients and risk of coronary artery disease and cardiac dysfunction—a retrospective propensity score analysis
1000 Autor/in
  1. Kattih, Badder |
  2. Shirvani, Amir |
  3. Klement, Piroska |
  4. Garrido, Abel Martin |
  5. Gabdoulline, Razif |
  6. Liebich, Alessandro |
  7. Brandes, Maximilian |
  8. Chaturvedi, Anuhar |
  9. Seeger, Timon |
  10. Thol, Felicitas |
  11. Göhring, Gudrun |
  12. Schlegelberger, Brigitte |
  13. Geffers, Robert |
  14. John, David |
  15. Bavendiek, Udo |
  16. Bauersachs, Johann |
  17. Ganser, Arnold |
  18. Heineke, Joerg |
  19. Heuser, Michael |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-09-18
1000 Erschienen in
1000 Quellenangabe
  • 35(5):1301-1316
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41375-020-01043-x |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102189/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Clonal 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.
1000 Sacherschließung
lokal Coronary Artery Disease/pathology [MeSH]
lokal Acute myeloid leukaemia
lokal Aged, 80 and over [MeSH]
lokal Coronary Artery Disease/genetics [MeSH]
lokal Aged [MeSH]
lokal Male [MeSH]
lokal Leukemia, Myeloid, Acute/genetics [MeSH]
lokal Stroke Volume [MeSH]
lokal Propensity Score [MeSH]
lokal Mutation/genetics [MeSH]
lokal Adolescent [MeSH]
lokal Female [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Retrospective Studies [MeSH]
lokal Middle Aged [MeSH]
lokal Article
lokal Coronary Artery Disease/etiology [MeSH]
lokal Cancer genetics
lokal Biomarkers, Tumor/genetics [MeSH]
lokal Prognosis [MeSH]
lokal Young Adult [MeSH]
lokal Genotype [MeSH]
lokal Ventricular Function, Left/genetics [MeSH]
lokal Isocitrate Dehydrogenase/genetics [MeSH]
lokal Leukemia, Myeloid, Acute/pathology [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-1324-5536|https://frl.publisso.de/adhoc/uri/U2hpcnZhbmksIEFtaXI=|https://frl.publisso.de/adhoc/uri/S2xlbWVudCwgUGlyb3NrYQ==|https://frl.publisso.de/adhoc/uri/R2FycmlkbywgQWJlbCBNYXJ0aW4=|https://frl.publisso.de/adhoc/uri/R2FiZG91bGxpbmUsIFJhemlm|https://frl.publisso.de/adhoc/uri/TGllYmljaCwgQWxlc3NhbmRybw==|https://frl.publisso.de/adhoc/uri/QnJhbmRlcywgTWF4aW1pbGlhbg==|https://orcid.org/0000-0002-9597-3010|https://frl.publisso.de/adhoc/uri/U2VlZ2VyLCBUaW1vbg==|https://frl.publisso.de/adhoc/uri/VGhvbCwgRmVsaWNpdGFz|https://frl.publisso.de/adhoc/uri/R8O2aHJpbmcsIEd1ZHJ1bg==|https://frl.publisso.de/adhoc/uri/U2NobGVnZWxiZXJnZXIsIEJyaWdpdHRl|https://orcid.org/0000-0003-4409-016X|https://frl.publisso.de/adhoc/uri/Sm9obiwgRGF2aWQ=|https://frl.publisso.de/adhoc/uri/QmF2ZW5kaWVrLCBVZG8=|https://orcid.org/0000-0002-9341-117X|https://frl.publisso.de/adhoc/uri/R2Fuc2VyLCBBcm5vbGQ=|https://orcid.org/0000-0002-1541-3030|https://orcid.org/0000-0001-5318-9044
1000 Hinweis
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1000 Erstellt am 2023-11-18T10:16:28.615+0100
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1000 Zuletzt bearbeitet 2023-12-01T13:30:18.511+0100
1000 Objekt bearb. Fri Dec 01 13:30:18 CET 2023
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