急性淋巴细胞白血病线粒体DNA突变的研究

目的:研究急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患者白细胞线粒体DNA D-loop区突变情况,以探讨线粒体DNA突变与急性白血病发生发展的关系。方法:采用聚合酶链反应-变性梯度凝胶电泳(polymerase chain reaction-denaturing gradient gel electrophoresis,PCR-DGGE)和DNA序列分析相结合的方法,对15例ALL病人治疗前、缓解期及复发时白细胞线粒体基因组的D-loop片段进行突变研究。结果:以缓解期为对照,发现8例(54%)ALL病人治疗前白细胞的线粒体DNA D-loop片段上出现突变,复发时又有相同或不同的突变出现;突变类型均为碱基替代突变,主要是C—T突变(43%);同时发现在线粒体DNA的某些位点发生突变的频率明显较高。结论:白细胞线粒体基因组的突变可能在白血病的发生发展过程中起重要作用。

Study on Mitochondrial DNA Mutation in ALL

Mutations in the D-loop of the mitochondrial genome were sought in 15 patients with acute lymphoblastic leukemia(ALL) by polymerase chain reaction-denaturing gradient gel electrophoresis(PCR-DGGE) and DNA sequencing.Comparison was made between DNA from marrow cells obtained at diagnosis,at remission,which was regarded as constitutional DNA,and at relapse.Mutations were detected at diagnosis in 8 of the patients with ALL(54%).Of these 8 patients,4 showed identical mutations at diagnosis and relapse and 4 showed a different pattern at relapse.Mutations were nearly always point mutation and the commonest mutations were C-T(43%).The distribution of mutations indicated a number of hot-spots.The results indicated that mitochondria mutations may play an important role in pathogenesis of leukemia and that at least some arise during growth of the leukemic clone.