WWOX和p73基因在急性髓细胞白血病中的表达

摘要

目的 研究WWOX(WW domain-containing oxidoreductase)和p73基因在急性髓细胞白血病(AML)中异常表达的临床意义及其机制.方法 收集AML患者骨髓58例,非白血病患者骨髓31例作为对照组,采用RT-PCR检测WWOX和p73基因mRNA的表达情况、甲基化特异性PCR检测WWOX基因启动子区和p73基因第一外显子区的甲基化情况.结果 58例AML患者中,28例WWOX基因mRNA阳性表达,30例p73基因mRNA阳性表达;23例WWOX基因启动子区存在甲基化,21例p73基因第一外显子区存在甲基化.对照组中WWOX与p73基因mRNA均有表达29例,均未见甲基化现象.WWOX和p73基因在AML中mRNA的表达以及甲基化状态与对照组比较差异均有统计学意义(P＜0.05).结论 WWOX与p73基因的甲基化可能导致其基因的沉默,使其mRNA表达减少或缺失,在AML的发病机制中起一定作用,WWOX与p73基因甲基化的检测对AML的诊断和疗效有一定意义.%Objective To investigate the significance of the abnormal expression of WWOX and p73 genes in acute myeloid leukemia ( AML ). Methods Bone marrows of 58 AML cases and 31 controls were collected. The mRNA of WWOX and p73 was assayed using reverse transcriptase -polymerase chain reaction, while methylation PCR was used to detect the promoter methylation of WWOX gene and the first exon of p73 gene. Results Among 58 AML patients, positive expression of WWOX and p73 mRNA was revealed in 28 and 30 cases, respectively. Methylation of WWOX gene promoter and the first exon of p73 gene were revealed in 23 and 21 patients with AML, respectively. Among 31 controls, positive expression of WWOX and p73 mRNA was revealed in 29 and 29 cases, respectively, whereas no methylation was found. There were significant differences in the expression of WWOX or p73 mRNA between AML group and control group, so was the methylation of WWOX or p73 gene ( P <0. 05 ). Conclusion The abnormal methylation of WWOX and p73 gene induces gene silence in AML, resulting in down - regulation of WWOX or p73 mRNA; suggesting this abnormal methylation is involved in the pathogenesis of AML. Detection of the methylation of WWOX and p73 can be applied in the diagnosis and the treatment evaluation of AML.