儿童急性淋巴细胞白血病p16基因甲基化及表达水平临床意义  

Clinical significance of methylation status and expression level of p16 gene in childhood acute lymphoblastic leukemia

作　　者：高源[1] 艾洪武[1] 金敏荣[1] 夏维[1] 代建红[1] 

机构地区：[1]武汉市儿童医院检验科,湖北武汉430016

出　　处：《国际检验医学杂志》2013年第1期46-48,共3页International Journal of Laboratory Medicine

摘　　要：目的探讨p16基因甲基化及表达水平改变在儿童急性淋巴细胞白血病(ALL)发病机制中的作用。方法 ALL患儿76例,其中初发(uALL)患儿69例、复发(rALL)患儿7例,健康儿童28例纳入对照组。采用荧光定量聚合酶链反应(RT-PCR)检测外周血淋巴细胞p16基因mRNA表达;采用基于SYBRGreen的甲基化特异性定量PCR(MethySYBRPCR)检测p16基因启动子甲基化水平。结果 ALL患儿淋巴细胞p16基因启动子甲基化水平高于健康儿童,uALL患儿p16基因甲基化水平低于rALL患儿(P<0.05);ALL患儿p16基因mRNA水平低于健康儿童,uALL患儿p16基因转录水平高于rALL患儿(P<0.05);p16基因转录水平与其启动子甲基化水平呈负相关关系(r=-0.63,P<0.05);首次化疗即获完缓解ALL患儿p16基因甲基化水平低于未完全缓解患儿,而p16mRNA表达水平高于后者(P<0.05);p16基因低甲基化或高表达水平ALL患儿巩固强化治疗平均缓解时间明显低于p16基因高甲基化或低表达患儿(P<0.05)。结论 p16基因甲基化及表达低下可能与ALL发病有关,p16基因甲基化状态及表达水平检测或可用于儿童ALL预后评估。Objective To investigate the effect of methylation status and expression level of p16 gene on pathogenesis and prognosis of childhood acute lymphoblastic leukemia（ALL）.Methods Seventy-six children with ALL and twenty-eight healthy children were enrolled and detected for expression level of p16 mRNA by real-time polymerase chain reaction（RT-PCR） and for the methylation status of CpG islands in promoter region of p16 gene by quantitative methylation-specific PCR based on SYBR Green（MethySYBR PCR） in peripheral blood mononuclear cells. Results CpG islands in p16 promoter were significantly methylated in children with ALL, while those in healthy volunteers were fully demethylated（P0.05）. Methylation level of p16 gene in untreated patients was higher than that in recurrent patients（P0.05）. Compared with healthy controls, transcriptional level of p16 gene in ALL patients decreased significantly（P0.05）, while expression level of p16 mRNA in untreated patients was higher than that in recurrent patients（P0.05）. Significant negative correlation between methylation level of p16 gene and its transcriptional level was observed in ALL patients（r=-0.63, P0.05）. After first chemotherapy, methylation level of p16 promoter in patients with complete remission was lower than that in patients with incomplete remission, while expression level of p16 mRNA in patients with complete remission was higher than that in patients with incomplete remission（P0.05）. During intensive consolidation chemotherapy, complete remission durations in patients with lower methylation levels or higher expression levels of p16 gene were lower than those with higher methylation levels or lower expression levels of p16 gene（P0.05）. Conclusion Methylation and transcription levels of p16 gene could play a role in pathogenesis of childhood ALL and might be regarded as a prognostic index.

关 键 词：P16基因 白血病 淋巴样 甲基化 儿童 

分 类 号：R733.71[医药卫生—肿瘤]