p73基因在成人急性淋巴细胞白血病中表达的研究

目的:研究p73基因在急性淋巴细胞性白血病(ALL)发病机制中的作用及临床意义。方法:收集32例ALL患者及30例正常对照组骨髓样本,DNA和RNA抽提后用RT-PCR检测p73基因的表达、甲基化特异性PCR(MSP)检测p73基因第一外显子甲基化状态,并结合临床资料进行分析。结果:11例p73基因阴性表达,阴性表达率为34.38%,其中9例第一外显子区域均发生甲基化(81.82%);21例p73基因阳性表达,32例ALL患者中,仅1例发生甲基化(4.76%);正常对照组30例,均为p73基因阳性表达,阳性表达率为100%。p73基因的阴性表达与ALL患者的高年龄(≥60岁)、高白细胞数(≥30×109/L)及对治疗时间延长(4周取得完全缓解)有关。结论:p73基因异常表达与成人ALL的发病机制有关,具有一定的诊断及判断预后的价值;其甲基化可能是p73基因在ALL中表达沉默的主要机制。

Abnormal Expression of p73 Gene in Adult Acute Lymphoblastic Leukemia

Objective：To investigate the effect of p73 gene on pathogenesis of acute lymphoblastic leukemia（ALL）and clinical significance of abnormal expression of p73 gene. Method：Genomic DNA and total RNA were extracted from 32 ALL and 30 normal bone marrow samples. The expression of p73 was evaluated by RT-PCR. The methylation specific PCR（MSP）was performed to examine the methylation status of p73 gene exon. Result：Of 32 ALL samples,11 showed without expression of p73 mRNA,with a negative rate of 34.38%. Normal samples all had expression of p73 gene,with a positive rate of 100%. 9 patients without expression of p73 were found to have methylation of p73 gene,whereas only one of patients with expression of p73 mRNA was found to have methylation. Negative expression of p73 gene was associated with higher age（≥60 years old ）,higher leucocyte count（≥30×109/L） and delayed reaction to therapy（patients attained complete remission after 4 weeks）. Conclusion：Negative expression of p73 gene probably plays a role in the diagnosis and pathogenesis of ALL,and might have clinical significance in predicting its prognosis. Methylation may be the major mechanism of gene silence of p73 in ALL.