抑癌基因Madl在白血病细胞中突变的研究

Mutation analysis of the tumor suppressor gene Madl in leukemia cells

目的:分析Madl基因突变在白血病发病中的作用机制。方法:利用逆转录-聚合酶链反应、单链构象多态性分析及DNA序列分析技术检测26例初治急性白血病患者,30名健康对照者和7种白血病细胞株Madl基因表达及突变情况。结果:RT-PCR显示所有标本中均可检测到Madl基因的表达,在7.7%(2/26)初治急性白血病患者中发现二处错义突变。结论:首次在急性白血病细胞中发现Madl基因突变,提示Madl基因的突变可能与白血病的发病有关。

Objective To detect the expression and mutation of Madl gene in fresh leukemia cells and leukemia cell line cells.Methods Expression and mutation of Madl gene in bone marrow mononuclear cells(BMMNC) from 26 de novo patients with acute leukemia(AL),and in peripheral blood mononuclear cells(PBMNC) from 30 healthy volunteers,as well as 7 human leukemic cell lines were analyzed by reverse transcription-polymerase chain reaction(RT-PCR),single strand conformational polymorphism(SSCP) and DNA sequencing.Results RT-PCR showed that all samples expressed Madl gene.Two missense mutations were detected in de novo AL patients.Among 26 de novo AL patients,2 patients were detected Madl mutation and the mutation rate was 7.7%.Conclusion For the first time,we demonstrated mutation of Madl gene in acute leukemia and the mutation of this gene may have a role in the pathogenesis of acute leukemia.