以免疫球蛋白和T细胞受体基因重排为标志定量检测MLL基因重排儿童急性淋巴细胞白血病的微小残留病和预后关系  

The detection of minimal residual disease using Immunoglobulin and T-cell receptor gene rearrangement based quantitative real time PCR and its clinical significance in children with MLL gene-rearranged acute lymphoblastic leukemia

作　　者：高超[1] 李伟京[1] 崔蕾[1] 赵晓曦[1] 刘曙光[1] 吴敏媛[1] 李志刚[1] 

机构地区：[1]首都医科大学附属北京儿童医院血液肿瘤中心,儿童血液病与肿瘤分子分型北京市重点实验室,教育部儿科重大疾病研究重点实验室,北京100045

出　　处：《中国循证儿科杂志》2013年第6期458-462,共5页Chinese Journal of Evidence Based Pediatrics

基　　金：国家自然科学基金项目:81300432;国家科技重大专项儿童白血病的国际化新药临床评价研究技术平台建设:2011ZX09302-007-01

摘　　要：目的探讨MLL基因重排儿童急性淋巴细胞白血病(ALL)微小残留病(MRD)与临床特征的关系及其对预后的指导作用。方法以2003年4月至2009年12月首都医科大学附属北京儿童医院血液肿瘤中心收治的MLL基因重排的ALL患儿为研究对象。以免疫球蛋白和T细胞受体基因重排、MLL融合转录本为标志,定量PCR方法监测MRD水平。以诱导治疗结束时MRD水平≥10-4为MRD阳性组,<10-4为MRD阴性组。卡方检验和Kaplan-Meier生存分析分别比较MRD阳性和阴性组临床特征和无事件生存率(EFS)的差异。结果 14例ALL患儿在诱导治疗结束时检测了MRD水平,MRD阳性组患儿初诊时外周血WBC计数显著高于MRD阴性组,对泼尼松实验治疗反应显著低于MRD阴性组。MRD阴性组5年EFS显著优于MRD阳性组,100%vs(37.5±17.1)%,P=0.022。结论诱导治疗结束时MRD水平有助于对MLL基因重排儿童ALL进行预后分组,指导个体化治疗、改善预后。Objective To discuss the correlation of minimal residual disease （MRD） and clinical characteristics as well as its prognostic significance in acute lymphoblastic leukemia （ALL） patients with MLL gene rearrangements. Methods The patients with ALL at Beijing Children＇s Hospital from May 2004 to December 2009 were enrolled. The MRD level was detected by real-time quantitative PCR method with immunoglobulin, T-cell receptor gene rearrangements and MLL fusion transcripts as targets. The differences of clinical characteristics and events free survival （EFS） rates between different MRD groups were compared with Chi- square and Kaplan-Meier method respectively. Results 14 cases were detected for MRD level at the end of induction therapy. Patients with high MRD level （ ≥ 10^-4 ） at the end of induction therapy had higher WBC counts at diagnosis and poorer prednisone responses than patients with low MRD level （ 〈 10 ^-4 ）. The different EFS rate was found in patients with different MRD level, a 5- year EFS rate of 100% in low level patients and （ 37.5 ± 17.1 ） % in high level group, respectively. Conclusion The MRD level at the end of induction therapy could distinguish the patients with different prognosis and implement the individual therapy to improve the patients＇outcomes.

关 键 词：急性淋巴细胞白血病 微小残留病 MLL基因重排 儿童 

分 类 号：R733.7[医药卫生—肿瘤]