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
Affiliations
- Mahmoud A. Bassal
- Harvard Stem Cell Institute, Harvard Medical School
- Saumya E. Samaraweera
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Kelly Lim
- Discipline of Medicine, University of Adelaide
- Brooks A. Bernard
- Hematology Division, Department of Medicine, Stanford Cancer Institute, Institute for Stem Cell and Regenerative Medicine, Stanford University
- Sheree Bailey
- Clinical and Health Sciences, University of South Australia
- Satinder Kaur
- Discipline of Medicine, University of Adelaide
- Paul Leo
- Diamantina Institute, Translational Research Institute
- John Toubia
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Chloe Thompson-Peach
- Discipline of Medicine, University of Adelaide
- Tran Nguyen
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Kyaw Ze Ya Maung
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Debora A. Casolari
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Diana G. Iarossi
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Ilaria S. Pagani
- Precision Medicine Theme, South Australian Health and Medical Research Institute
- Jason Powell
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Stuart Pitson
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Siria Natera
- Metabolomics Australia, The University of Melbourne
- Ute Roessner
- Metabolomics Australia, The University of Melbourne
- Ian D. Lewis
- Adelaide Oncology & Haematology
- Anna L. Brown
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Daniel G. Tenen
- Harvard Stem Cell Institute, Harvard Medical School
- Nirmal Robinson
- Centre for Cancer Biology, University of South Australia and SA Pathology
- David M. Ross
- Centre for Cancer Biology, University of South Australia and SA Pathology
- Ravindra Majeti
- Hematology Division, Department of Medicine, Stanford Cancer Institute, Institute for Stem Cell and Regenerative Medicine, Stanford University
- Thomas J. Gonda
- Clinical and Health Sciences, University of South Australia
- Daniel Thomas
- Discipline of Medicine, University of Adelaide
- Richard J. D’Andrea
- Centre for Cancer Biology, University of South Australia and SA Pathology
- DOI
- https://doi.org/10.1038/s41467-022-30223-9
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 12
Abstract
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.
