Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
Eur J Haematol. 2013 May;90(5):385-96. doi: 10.1111/ejh.12090. Epub 2013 Mar 22.
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.
最近的研究表明，线粒体基因组（mtDNA）的突变可能在人类癌症的发展和治疗反应中起作用。本研究旨在探讨 mtDNA 变异是否具有任何预后相关性，阐明 mtDNA 变异的谱，并确定其是否与急性髓细胞白血病（AML）中的已知预后因素有关。为了阐明这一点，我们对 56 名 AML 患者和 14 名对照进行了整个 mtDNA 的测序。在分析 mtDNA 编码基因中非同义变异的生物学影响时，我们发现对氧化磷酸化复合物（OXPHOS）中两个最重要的催化基因（细胞色素 c 氧化酶亚基 I 和细胞色素 c 氧化酶亚基 II）发生变异的患者无病生存率降低（危险比 2.6，P=0.03；多变量分析）。此外，在调控区发现的最常见变异是 T16311C，在 56 名患者中的 11 名（20%）中发现了该变异。这一观察结果在另一个由 173 例诊断性 AML 样本组成的队列中得到了证实。在这个扩展组中，T16311C 变异倾向于与染色体异常相关。
