Nature Communications (May 2022)

Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia

  • Mahmoud A. Bassal,
  • Saumya E. Samaraweera,
  • Kelly Lim,
  • Brooks A. Bernard,
  • Sheree Bailey,
  • Satinder Kaur,
  • Paul Leo,
  • John Toubia,
  • Chloe Thompson-Peach,
  • Tran Nguyen,
  • Kyaw Ze Ya Maung,
  • Debora A. Casolari,
  • Diana G. Iarossi,
  • Ilaria S. Pagani,
  • Jason Powell,
  • Stuart Pitson,
  • Siria Natera,
  • Ute Roessner,
  • Ian D. Lewis,
  • Anna L. Brown,
  • Daniel G. Tenen,
  • Nirmal Robinson,
  • David M. Ross,
  • Ravindra Majeti,
  • Thomas J. Gonda,
  • Daniel Thomas,
  • Richard J. D’Andrea

DOI
https://doi.org/10.1038/s41467-022-30223-9
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 12

Abstract

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Mitochondrial metabolism has been associated with tumourigenesis in acute myeloid leukaemia (AML) and currently considered as a potential therapeutic target. Here, the authors show, in patients with AML, that germline mutations in mitochondrial complex I are mutually exclusive with somatic mutations in the metabolic enzyme IDH1, and find IDH1 mutant cells have increased sensitivity to complex I inhibitors.