Somatic mitochondrial DNA mutations in adult-onset leukaemia

He, Langping; Luo, Lin; Proctor, S J; Middleton, PG; Blakely, Emma L.; Taylor, Robert W.; Turnbull, D.M.

doi:10.1038/sj.leu.2403146

Cited by 71 publications

(59 citation statements)

References 36 publications

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“…Mitochondrial DNA variant sequences were proposed as natural genetic markers for determining the contribution of individual stem cells to blood production. In addition, mtDNA changes fixed in leukemic cells might provide a simple method for monitoring minimal residual disease (He et al, 2003).…”

Section: Mitochondrial Dna Mutations In Hematopoietic Cell Aging and mentioning

confidence: 99%

Mitochondria in hematopoiesis and hematological diseases

et al. 2006

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Section: Mitochondrial Dna Mutations In Hematopoietic Cell Aging and mentioning

confidence: 99%

Mitochondria in hematopoiesis and hematological diseases

et al. 2006

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“…8 Furthermore, mtDNA mutations have been reported in bone marrow failure syndromes such as Pearson's syndrome, 13 and in de novo and secondary AML. 6,14,15 Many of these mutations involve mitochondrial genes encoding components of respiratory Complex I of the electron transport chain. Complex I is located within the mitochondrial inner membrane and is the initiating step in the electron transport chain of mitochondrial oxidative phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

Prognostic implications and molecular associations of NADH dehydrogenase subunit 4 (ND4) mutations in acute myeloid leukemia

et al. 2011

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To study the prevalence and prognostic importance of mutations in NADH dehydrogenase subunit 4 (ND4), a mitochondrial encoded transmembrane component of the electron transport chain respiratory Complex I, 452 AML patients were examined for ND4 mutations by direct sequencing. The prognostic impact of ND4 mutations was evaluated in the context of other clinical prognostic markers and genetic risk factors. In all, 29 of 452 patients (6.4%) had either somatic (n ¼ 12) or germline (n ¼ 17) ND4 mutations predicted to affect translation. Somatic mutations were more likely to be heteroplasmic (Po0.001), to occur in predicted transmembrane domains (Po0.001) and were predicted to have damaging effects upon translation (Po0.001). Patients with somatically acquired ND4 mutations had significantly longer relapse-free survival (P ¼ 0.017) and overall survival (OS) (P ¼ 0.021) than ND4 wildtype patients. Multivariate analysis also demonstrated a tendency for increased survival in patients with somatic ND4 mutations (RFS: hazard ratio (HR) 0.25, confidence interval (CI) 0.06-1.01, P ¼ 0.052; OS: HR 0.29, CI 0.74-1.20, P ¼ 0.089). Somatic ND4 mutated patients had a higher prevalence of concomitant DNMT3A mutations (P ¼ 0.023) and a higher percentage of the NPM1/FLT3-ITD lowrisk genotype (P ¼ 0.021). Germline affected cases showed higher BAALC (P ¼ 0.036) and MLL5 (P ¼ 0.051) expression levels. Further studies are warranted to validate the favorable prognostic influence of acquired ND4 mutations in AML.

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“…Since many mtDNA mutations identified in solid tumors or clonal bone marrow disorders are silent mutations or mutations changing poorly conserved nucleotides or amino acids, 48,1 it is inappropriate to claim that mtDNA mutations play an important general role in carcinogenesis or leukemogenesis. On the other hand, it is equally unjustified to claim that all mtDNA mutations are irrelevant.…”

Section: Mtdna Mutations In the Context Of Clonal Bone Marrow Disordersmentioning

confidence: 99%

Mitochondrial DNA mutations in the hematopoietic system

Gattermann

2003

Leukemia

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Somatic mitochondrial DNA mutations in adult-onset leukaemia

Cited by 71 publications

References 36 publications

Mitochondria in hematopoiesis and hematological diseases

Mitochondria in hematopoiesis and hematological diseases

Prognostic implications and molecular associations of NADH dehydrogenase subunit 4 (ND4) mutations in acute myeloid leukemia

Mitochondrial DNA mutations in the hematopoietic system

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