Linnartz Bjoern, Anglmayer Roswitha, Zanssen Stefanie
Department of Biochemistry, Medical Faculty, Rheinisch Westfaelische Technische Hochschule Aachen, Aachen, Germany.
Cancer Res. 2004 Mar 15;64(6):1966-71. doi: 10.1158/0008-5472.can-03-2956.
Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterized by ineffective hematopoiesis resulting in refractory cytopenias. Transformation resulting in acute myeloblastic leukemia is the final stage in the multistep process of MDS evolution. Functional relevant mutations of mitochondrial DNA (mtDNA) have been related to sideroblastic anemia and MDS. To investigate the role of mtDNA in malignant transformation to acute leukemia, we used high-resolution techniques such as single-strand conformational polymorphism and fluorescence sequencing for investigation of the whole mitochondrial genome from blood cells of 10 patients with MDS. Functionally relevant point mutations in mitochondrial RNA and polypeptide-encoding genes were detected in 50% of patients with MDS. Their increasing mutation load connects MDS and the developing acute myeloid leukemias. Several point mutations of mtDNA, including secondary point mutations for Leber's hereditary optic neuropathy, occur in one bone marrow and may synergically affect bone marrow stem cells by an apoptotic pathway.
骨髓增生异常综合征（MDS）是一种克隆性髓系疾病，其特征为造血功能无效导致难治性血细胞减少。向急性髓细胞白血病的转化是MDS演变多步骤过程的最后阶段。线粒体DNA（mtDNA）的功能相关突变与铁粒幼细胞贫血和MDS有关。为了研究mtDNA在向急性白血病恶性转化中的作用，我们使用了高分辨率技术，如单链构象多态性和荧光测序，来研究10例MDS患者血细胞的整个线粒体基因组。在50%的MDS患者中检测到线粒体RNA和多肽编码基因的功能相关点突变。它们不断增加的突变负荷将MDS与正在发展的急性髓细胞白血病联系起来。mtDNA的几个点突变，包括Leber遗传性视神经病变的继发性点突变，出现在一个骨髓中，并可能通过凋亡途径协同影响骨髓干细胞。
