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

• Published in: Nature communications Vol. 13; no. 1; p. 2614
• Main Authors: Bassal, Mahmoud A., Samaraweera, Saumya E., Lim, Kelly, Benard, Brooks A., Bailey, Sheree, Kaur, Satinder, Leo, Paul, Toubia, John, Thompson-Peach, Chloe, Nguyen, Tran, Maung, Kyaw Ze Ya, Casolari, Debora A., Iarossi, Diana G., Pagani, Ilaria S., Powell, Jason, Pitson, Stuart, Natera, Siria, Roessner, Ute, Lewis, Ian D., Brown, Anna L., Tenen, Daniel G., Robinson, Nirmal, Ross, David M., Majeti, Ravindra, Gonda, Thomas J., Thomas, Daniel, D’Andrea, Richard J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/31; 13/44; 45/23; 631/67/2327; 631/67/68; 692/4028/67/1990/283/1897; Acute myeloid leukemia; Adult; Citric acid; Electron transport chain; Epistasis; Genomics; Germ-Line Mutation; Humanities and Social Sciences; Humans; Inhibitors; Isocitrate dehydrogenase; Isocitrate Dehydrogenase - genetics; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Metabolism; Mitochondria; Mitochondrial DNA; multidisciplinary; Mutants; Mutation; NADH-ubiquinone oxidoreductase; Science; Science (multidisciplinary); Sensitivity; Therapeutic targets

The interaction of germline variation and somatic cancer driver mutations is under-investigated. Here we describe the genomic mitochondrial landscape in adult acute myeloid leukaemia (AML) and show that rare variants affecting the nuclear- and mitochondrially-encoded complex I genes show near-mutual...