儿童急性髓系白血病基因拷贝数变异的临床研究

Copy Number Variations in Pediatric Acute Myeloid Leukemia

目的:研究儿童急性髓系白血病(AML)中基因拷贝数变异的发生率及其与临床特征及预后的相关性。方法:回顾性分析130例AML患儿临床资料,包括临床特征、FAB分型及细胞遗传学改变等。收集130例AML患儿和38例健康志愿儿童的骨髓或外周血,常规提取基因组DNA。应用多重连接探针扩增法(MLPA)检测多个基因拷贝数变异的情况。利用SPSS16.0软件进行统计学分析。结果:在130例患儿中,超过10%的拷贝数变异涉及的染色体区段为2p24.3(MYCN)、10q23(PTEN)和13q14(RB1,MIR15A,DLEU);在49例(37.7%)患者中检测到基因探针的扩增和缺失,涉及改变的基因探针个数的中位数为4个。TP53探针发生缺失/扩增的患儿复发率高。各探针发生缺失/扩增对EFS、DFS及OS均无影响。12%的患儿存在基因组异常,用常规染色体核型的方法不能检出。结论:MLPA技术可作为染色体核型检测的补充。TP53拷贝数异常的儿童AML患者易发生复发。

Objective： To evaluate the copy number variations （CNV） of gene in pediatric acute myeloid leukemia （AML） and its correlation with clinical features and prognosis. Methods：The clinical data of 130 children aged 〈 14 years with newly diagnosed AML from May 2006 to March 2013 were analyzed restrospectively. The CNV were analyzed by multiplex ligation-dependent probe amplification （MLPA）. Thirty-eight normal children were selected in control group. All the data were statistically analyzed using SPSS16.0 software. Results： gene CNV of 2p24. 3 （ MYCN）, 10q23 （PTEN） and 13q14 （ RB1, MIR15A, DLEU） were detected in more than 10% of the patients. CNV were detected in 49 cases（37.7% ）. The median loss and gain CNV frequencies per sample were 4. The CNV of TP53 correlated significantly with relapse. The loss ond gain CNV have no influence to EFS, DSF and OS. CNV were detected in the twelve percent of patients, but they were not detected with routine karyotype method. Conclusion：The MLPA technique combined with karyotyping makes a substantial increase in the diagnostic rate. Patients with TP53 alterations have significantly higher relapse rate.