p73基因DNA甲基化与儿童急性白血病的关系

Relationship between DNA methylation of p73 gene and acute leukemia of children

目的探讨p73基因DNA甲基化在儿童急性白血病发病中的作用。方法选取142例(年龄<15岁)初发急性白血病儿童作为病例组,其中急性淋巴细胞白血病(ALL)112例,急性髓性白血病(AML)30例;以接受健康体检或就诊的性别、年龄匹配的123儿童(排除血液系统疾病和肿瘤性疾病)作为对照组。采用甲基化特异性聚合酶链反应(MSP)分析病例组与对照组儿童p73基因的甲基化状态。随机选取p73基因DNA甲基化片段与非甲基化片段样本各1例进行PCR产物序列分析。结果病例组p73基因DNA甲基化发生率(7.7%)显著高于对照组(0.8%),差异有统计学意义(P<0.05);病例组和对照组p73基因缺失率分别为6.3%和4.1%,组间比较差异无统计学意义(P>0.05)。病例组中ALL患儿的p73基因DNA甲基化发生率为8.9%,显著高于对照组(P<0.01)。随机选取的2个样本的测序结果与MSP结果一致。结论 p73基因DNA甲基化可能在儿童急性白血病尤其是ALL的发病中发挥重要作用。

Objective To investigate the relationship between DNA methylation of p73 gene and acute leukemia of children. Methods One hundred and forty-two children with newly diagnosed acute leukemia aged less than 15 years were selected as case group,among whom 112 were acute lymphoblastic leukemia(ALL) and 30 were acute myeloid leukemia(AML).Another 123 sex and age-matched children undergoing physical examinations,outpatient visit or treatment without hematological diseases and tumors were served as control group.The methylation status of p73 gene of children in case group and control group was analysed by methylation-specific polymerase chain reaction(MSP).One sample of DNA methylated fragment and one sample of DNA non-methylated fragment of p73 gene were randomly selected for sequencing analysis of PCR product. Results The prevalence of DNA methylation of p73 gene in case group was significantly higher than that in control group(7.7% vs 0.8%,P<0.05),while there was no significant difference in the deletion rate of p73 gene between case group and control group(6.3% vs 4.1%,P>0.05).The prevalence of DNA methylation of p73 gene in children with ALL in case group(8.9%) was significantly higher than that in control group(P<0.01).The sequencing results of two randomly selected samples were consistent with results of MSP. Conclusion DNA methylation of p73 gene may play an important role in the development of acute leukemia of children,especially in the development of ALL.