儿童ETV6／RUNX1阳性急性淋巴细胞性白血病基因拷贝数变异的临床研究

Copy number variations in pediatric ETV6/RUNX1 positive acute lymphoblastic leukemia

目的探讨ETV6／RUNXl阳性急性淋巴细胞性白血病（ALL）患儿基因拷贝数变异与临床特征及预后的相关性。方法回顾性分析2006年1月至2012年11月于中国医学科学院血液病医院就诊的141例ETV6／RUNXl阳性ALL患儿临床资料，并进行随访。应用多重连接探针扩增（MLPA）技术检测多个基因拷贝数变异的情况，探讨不同基因拷贝数变异的患儿的生存率。结果141例ETV6／RUNXl阳性的ALL患儿，其中男78例（55．3％）、女63例（44．7％），中位年龄4（1—13）岁，5年无复发生存率（RFS）为（85±4）％，无病生存率（DFS）为（844-4）％，5年总生存率（0s）为（85±4）％。95例患儿进行了MLPA检测，73例（76．8％）患儿检测到基因拷贝数的改变。拷贝数变异率超过10％的基因为EBF1（15．8％）、CDKN2A／2B（18．9％）、PAX5（21．1％）、ETV6（54．8％）、BTGl（10．5％）。95例患儿中，9例出现EBF1基因的缺失，80例EBF1基因正常，6例EBF1基因扩增，各组患儿5年无复发生存率（RFS）差异有统计学意义（χ2=9．809，P=0．007）；13例出现PAX5基因的缺失，75例PAX5基因正常，7例PAX5基因扩增，各组患儿5年无复发生存率（RFS）差异有统计学意义（χ2=7．622，P=0．022）；39例出现ETV6基因的缺失，43例E＇IW6基因正常，13例ETV6基因扩增，各组患儿5年无复发生存率（RFS）差异有统计学意义（χ2=11．045，P=0．004）。结论基因拷贝数改变与ETV6／RUNXl阳性Au．的临床特征和预后有一定的相关性。EBF1扩增、PAX5扩增、ETV6扩增的患儿易发生复发。

Objective To evaluate the copy number variations （CNVs） in pediatric ETV6/RUNX1 gene positive acute lymphoblastic leukemia （ALL） and its correlation with clinical features and prognosis. Method Totally 141 children （ 〈 14 years of age） with newly diagnosed ETV6/RUNX1 positive ALL in Institute of Hematology and Blood Diseases Hospital, were included from January 2006 to November 2012. The CNVs were analyzed by multiplex ligation-dependent probe amplification （MLPA）. The survival rate between the patients with CNVs were explored. Overall survival （OS） and event-free survival （EFS） were estimated by the Kaplan-Meier method and compared with the log-rank test. Result Among the 141 cases, 55.3% （ n = 78 ） were boys and 44. 7% （ n = 63 ） were girls and the median age was 4 （ 1 - 13 ） years. The estimated 5-year DFS rate for the patients was （ 84 ± 4） %. The estimated 5-year OS rate for the patients was （85 ±4）%. Ninety-five patients were tested MLPA. CNVs were detected in 73 cases （76. 8% ）. CNVs of genes EBF1 （15.8%）, CDKN2A/2B（18.9% ）, PAXS（21.1% ）, ETV6（54. 8% ）, BTG1 （10. 5% ） were detected in more than 10% of the patients. Among the 95 patients, EBF1 deletions were found in 9 patients and EBF1 amplifications were found in 6 patients; 5-year recurrence-free survival （RFS） was statistically significant among 3 groups （ χ2 = 9. 809 ,P -- 0. 007 ） . PAX5 deletions were found in 13 patients and PAX5 amplifications were found in 7 patients; the difference in 5-year RFS was statistically significant between 3 groups（ χ2 = 7. 622,P = 0. 022）. ETV6 deletions were found in 39 patients and ETV6 amplifications were found in 13 patients; the difference in 5-year RFS was statistically significant among the 3 groups （χ2=11. 045 ,P = 0. 004）. Conclusion The CNVs had prognostic re｜evance in ETV6/RUNX1 positive ALL.