Bim基因内含子缺失多态性在儿童急性淋巴细胞白血病治疗中的临床意义  

Clinical significance of Bim deletion polymorphism in the treatment of childhood acute lymphoblastic leukemia

作　　者：汤燕静[1] 王翔[1] 沈树红[1] 陈静[1] 薛惠良[1] 潘慈[1] 汤静燕[1] 

机构地区：[1]上海交通大学医学院附属上海儿童医学中心血液肿瘤科,国家卫计委儿童血液肿瘤重点实验室,上海200127

出　　处：《中国小儿血液与肿瘤杂志》2016年第4期174-177,198,共5页Journal of China Pediatric Blood and Cancer

基　　金：上海市卫生和计划生育委员会项目(20124136)

摘　　要：目的探讨Bim基因内含子缺失多态性在儿童急性淋巴细胞白血病糖皮质激素治疗中的临床意义。方法提取入组110例缓解期儿童急性淋巴细胞白血病患儿骨髓液并提取基因组DNA,采用PCR方法特异性扩增基因组DNA检测,是否存在Bim基因内含子2序列缺失并行Sanger测序鉴定。分析Bim基因内含子缺失与泼尼松反应和远期预后之间的关系。结果 110例患儿中,共有17例存在Bim内含子2的部分序列缺失,占15.4%,其5年无事件生存率为68.0%(SE=0.122),与无序列缺失患儿(5年EFS为69.6%,SE=0.048)无明显差异(P=0.940);单因素分析提示泼尼松敏感试验与Bim缺失多态无相关性(P=0.451),与患儿年龄、性别、免疫表型、化疗第35天微小残留病(MRD)、诊断时外周血白细胞数也无显著统计学差异(P值分别为0.224、0.784、1.000、0.716、0.604),但是与儿童急性淋巴细胞白血病危险度分组相关(P=0.046)。结论Bim基因内含子缺失多态性与ALL患儿糖皮质激素耐药和远期预后无显著相关性。Objective To explore the clinical significance of intronic deletion polymorphism in the gene encoding BCL2-like 11（BIM） in children with acute lymphoblastic leukemia（ALL）.Methods Germline genomic DNA was extracted from remission bone marrow samples of 110 ALL cases recruited from May 2005 to Apr 2009.PCR reactions were run by primer pare flunk the deletion site of BIM to discriminate polymorphism by products size.The relationship between BIM deletion polymorphism and therapeutic outcome including prednisone response and 5-year event-free survival（EFS） was analyzed.Results Among these 110 patients,72 were male,38 were female.The medium age was 5（range0.5-16） years.53 patients were low-risk,52 intermediate-risk and 5 high-risk.On Day 8 of induction,96 patients were classified as prednisone good response（PGR） and 14 were prednisone poor response（PPR）.The BIM deletion polymorphism was present in 17 cases.The Kaplan-Meier estimated 5-year EFS was 68.0%in these 17 cases and there was no significant difference between cases with or without deletion polymorphism（P = 0.940）.Mono-variable analysis showed there was no correlation between BIM deletion polymorphism and prednisone response（P =0.451）.Neither with other prognostic factors including age,gender,immunophenotype,minimal residual disease（MRD） on day 35 of induction,and peripheral white blood cell count at diagnosis（P = 0.224,0.784,1.000,0.716,0.604）.But high risk group tended to have more deletion polymorphism.（P =0.046）.Conclusions Subtle correlation between the BIM intron deletion polymorphism and treatment and prognosis were seen in children with ALL.

关 键 词：Bim基因 糖皮质激素 治疗 白血病 淋巴细胞性 儿童 

分 类 号：R733.71[医药卫生—肿瘤]