定量多色FISH检测儿童ETV6-RUNX1阳性急性淋巴细胞白血病的异质性及克隆演化  

Heterogeneity and clonal evolution in pediatric ETV6-RUNX1^＋ acute lymphoblastic leukemia by quantitative multigene fluorescence in situ hybridization

作　　者：张丽 胡林萍 刘晓明 郭晔 杨文钰 张家源 刘芳[1] 刘天峰 王书春 陈晓娟 阮敏 戚本泉 常丽贤 陈玉梅 邹尧 竺晓凡 

机构地区：[1]中国医学科学院、北京协和医学院血液学研究所、血液病医院,天津300020

出　　处：《中华血液学杂志》2017年第7期586-591,共6页Chinese Journal of Hematology

基　　金：基金项目：国家自然科学基金（81200396、81470339）;天津市科技支撑计划（12ZCDZSY18100）;天津市卫生计生委科技基金重点项目（2014KR12）;天津市疾病预防控制中心科技基金项目（CDCKY1406）

摘　　要：【摘要】目的研究儿童ETV6-RUNX1阳性急性淋巴细胞白血病（ALL）中肿瘤细胞的异质性及克隆演化情况，探讨克隆演化与预后的相关性。方法应用单细胞定量多基因荧光原位杂交（QM—FISH）技术对2006年2月至2011年6月收治的48例ETV6-RUNX1阳性ALL患儿的骨髓标本进行多个基因拷贝数变异的检测，并进行克隆演化分析。将4例复发患儿初诊与复发时的情况进行比较。结果在48例行QM—FISH检测的患儿中，初诊时为1个克隆的有34例（70．8％），2个克隆的有9例（18．8％），i〉3个克隆的有5例（10．4％）。患儿的肿瘤细胞存在异质性，各亚克隆之间呈线性或树枝状演化。白血病细胞的亚克隆数与患者预后无相关性（5年总生存率：P=0．469；5年无病生存率：P=-0．116）。复发克隆可能与初诊时克隆一致，也可能为新出现克隆。复发克隆为新出现克隆的患儿再次缓解时间短，预后更差。结论ETV6-RUNX1阳性ALL患儿肿瘤细胞存在异质性及克隆演化情况。QM—FISH有助于研究白血病细胞的克隆演化，复发克隆为新出现克隆的患儿可能预后更差。Objective To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1 ＋ acute lymphoblastic leukemia （ALL） in China. Methods Totally 48 children （ 〈14 years） with newly diagnosed ETV6-RUNX1 ＋ ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization （QM-FISH） in 48 patients. Non-normal distribution of measurement data were shown with Median （range）, count data were shown with percent （%）. Overall survival and event-free survival were estimated by the Kaplan-Meier method and compared with the log-rank test. Results Forty-eight patients were tested by QM-FISH. Of 48 patients, 70.8% harbored one clone, 18.8% two subclones, and 10.4% three or more subclones. The clone heterogeneity was detected by two different models： the linear succession model and the branching evolution model. ETV6- RUNX1 ＋ ALL relapse evolved from an ancestral clone or a new clone. The patients relapsed from a new clone got the worse outcome. Conclusion The clone evolution was detected in pediatric ETV6-RUNXI^＋ ALL in China. QM-FISH might be helpful to evaluate the outcome of relapsed patients. A new clone was associated with a poorer outcome.

关 键 词：儿童 白血病 淋巴细胞 急性 DNA拷贝数异常 

分 类 号：R733.71[医药卫生—肿瘤]