title: Characterization and prognostic significance of mitochondrial DNA variations in acute myeloid leukemia.
abstract: Recent studies have suggested that mutations in the mitochondrial genome (mtDNA) may play a role in the development and response to treatment for human cancer. The aim of this study was to investigate whether mtDNA variations have any prognostic relevance, to clarify the spectra of mtDNA variation and to determine whether there was any correlation to known prognostic factors in acute myeloid leukemia (AML). To elucidate this, we sequenced the entire mtDNA in 56 AML patients and 14 control subjects. When analyzing the biologic impact of the non-synonymous variations in the mtDNA coding genes, we found an inferior disease-free survival for patients exhibiting variations in the two most important catalytic genes of the complex IV of the oxidative phosphorylation complexes (OXPHOS), that is, the cytochrome c oxidase subunit I and the cytochrome c oxidase subunit II (hazard ratio 2.6, P = 0.03; multivariate analysis). In addition, the most frequent variation was the T16311C in the control region, which was found in 11 (20%) of the 56 patients. This observation was confirmed in another cohort of 173 diagnostic AML samples. In this expanded group, the T16311C variation tended to be associated with chromosomal abnormalities.
authors: Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
authors: Trine
authors: T
authors: Silkjaer
authors: Jan Maxwell
authors: JM
authors: Nørgaard
authors: Anni
authors: A
authors: Aggerholm
authors: Lene Hyldahl
authors: LH
authors: Ebbesen
authors: Eigil
authors: E
authors: Kjeldsen
authors: Peter
authors: P
authors: Hokland
authors: Charlotte Guldborg
authors: CG
authors: Nyvold
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D004272:DNA, Mitochondrial; D005260:Female; D050259:Genes, Mitochondrial; D014644:Genetic Variation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011379:Prognosis; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial