Zhang Ao, Liu Wenbing, Qiu Shaowei
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Tianjin Institutes of Health Science, Tianjin, China.
Blood Sci. 2024 Sep 5;6(4):e00205. doi: 10.1097/BS9.0000000000000205. eCollection 2024 Oct.
Leukemias are a group of heterogeneous hematological malignancies driven by diverse genetic variations, and the advent of genomic sequencing technologies facilitates the investigation of genetic abnormalities in leukemia. However, these sequencing-based studies mainly focus on nuclear DNAs. Increasing evidence indicates that mitochondrial dysfunction is an important mechanism of leukemia pathogenesis, which is closely related to the mitochondrial genome variations. Here, we provide an overview of current research progress concerning mitochondrial genetic variations in leukemia, encompassing gene mutations and copy number variations. We also summarize currently accessible mitochondrial DNA (mtDNA) sequencing methods. Notably, somatic mtDNA mutations may serve as natural genetic barcodes for lineage tracing and longitudinal assessment of clonal dynamics. Collectively, these findings enhance our understanding of leukemia pathogenesis and foster the identification of novel therapeutic targets and interventions.
白血病是一组由多种基因变异驱动的异质性血液系统恶性肿瘤，基因组测序技术的出现促进了对白血病基因异常的研究。然而，这些基于测序的研究主要集中在核DNA上。越来越多的证据表明，线粒体功能障碍是白血病发病机制的重要机制，这与线粒体基因组变异密切相关。在此，我们概述了目前关于白血病线粒体基因变异的研究进展，包括基因突变和拷贝数变异。我们还总结了目前可获得的线粒体DNA（mtDNA）测序方法。值得注意的是，体细胞mtDNA突变可作为谱系追踪和克隆动态纵向评估的天然遗传条形码。总的来说，这些发现加深了我们对白血病发病机制的理解，并促进了新型治疗靶点和干预措施的识别。
