Characterization of Mutations in the Mitochondrial Encoded Electron Transport Chain Complexes in Acute Myeloid Leukemia.

ABSTRACT: Acute Myeloid Leukemia is a devastating and heterogeneous, hematological malignancy characterized by the uncontrolled proliferation of undifferentiated myeloid progenitor cells-blasts. Mutations in certain mitochondrial proteins, such as IDH2 have been shown to contribute to leukemogenesis. However, the role of mutations in mitochondrial-encoded Electron Transport Chain (ETC) genes have thus far not been well elucidated in AML. Here, we use TCGA data to characterize mutations in the ETC genes and their association with clinical outcomes in AML. We found that mitochondrial ETC mutations-in Complex I, III, IV and/or V (ATP Synthase)-were present in 8% of patients with AML and were significantly more frequent in older patients. Patients with ETC mutations had worse overall survival than ETC wild type patients (OS: 9.3 vs 20.1 months; p-value: 0.007). Additionally, mutations in either or both Complex I and IV were associated with TP53 mutations (p-value: 0.009), and among TP53 mutated patients, mutations in either or both Complex I and IV were significantly associated with worse overall survival (OS: 0.85 vs 9.4 months; p-value: 0.008). Elucidation of the mechanisms by which ETC mutations contribute to AML pathogenesis and progression would facilitate the development of novel therapeutic targets.

SUBMITTER: Wu S 

PROVIDER: S-EPMC6125587 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature