儿童急性淋巴细胞白血病患者p73基因异常表达的研究  

Study on abnormal expression of the p73 gene in childhood acute lymphoblastic leukemia

作　　者：刘明利[1] 李蓉生[1] 林泰秀[2] 竹谷健[2] 郭山春[2] 

机构地区：[1]中国医学科学院,中国协和医科大学北京协和医院,北京100730 [2]日本东京大学附属病院

出　　处：《中华血液学杂志》2002年第5期239-242,共4页Chinese Journal of Hematology

摘　　要：目的　探讨儿童急性淋巴细胞白血病 (ALL)发生及发展的机制。方法　应用RT PCR技术检测 61个ALL细胞系和 53例儿童ALL患者的p73基因mRNA表达情况 ,并结合患者的临床资料进行分析。应用DNA甲基化酶谱测定、亚硫酸氢钠修饰的PCR和PCR产物测序等技术对 61个ALL细胞系p73基因第 1外显子的甲基化进行检测。结果　 61个ALL细胞系中p73mRNA阴性表达率为31 1 % (61个中 1 9个 ) ;53例原发性儿童ALL患者中 ,p73mRNA阴性表达率为 2 6 .4 % (53例中 1 4例 ) ,p73mRNA阴性表达与ALL无病生存期、总生存期的降低有明显关系。 61个ALL细胞系中 ,39.3 %存在p73基因的高甲基化。正常淋巴细胞和不存在p73基因高甲基化的细胞系表达p73mRNA ,大多数高甲基化的细胞系不表达p73mRNA。结论　儿童ALL患者中p73mRNA存在较高的阴性表达 ,其主要机制为p73基因高甲基化 ,p73基因失活在ALL的发生及发展中起重要作用 。Objective To investigate the relationship between p73 gene and the development and progression of childhood acute lymphoblastic leukemia (ALL). Methods The levels of p73 transcripts in 61 ALL cell lines and 53 childhood ALL patients were assayed using reverse transcriptase polymerase chain reaction (RT PCR), and their relationship with the clinicopathological characteristics was analyzed. Besides, the methylation status of p73 exon 1 was analysed by restriction enzyme related PCR, methylation specific PCR and bisulfite genomic sequencing in the 61 ALL cell lines. Results Of the 61 ALL cell lines, 42 showed expression of p73 mRNA, with a negative rate of 31.1%, and of the 53 primary childhood ALL samples, 39 showed expression of p73 mRNA, with a negative rate of 26.4%. Loss of p73 expression was significantly associated with the reduced disease free survival and overall survival of the patients. 39.3 % (24/61) of the ALL cell lines showed hypermethylation of p73 exon 1, while normal lymphocytes and most cell lines expressed p73 mRNA were not hypermethylated. Conclusion There was a higher negative expression rate of p73 mRNA in childhood ALL. The main mechanism of the loss expression would be the hypermethylation of p73 gene. p73 gene inactivation might play an important role in the pathogenesis of ALL. Examination of p73 mRNA might have clinical significance in predicting prognosis of childhood ALL.

关 键 词：儿童 急性淋巴细胞白血病 P73基因 甲基化 基因表达 

分 类 号：R733.7[医药卫生—肿瘤]