胸苷酸合成酶基因多态性对甲氨喋呤治疗急性淋巴细胞白血病患儿不良反应的影响  

Influence of thymidylate synthase gene polymorphisms on high-dose methotrexaterelated toxicities in childhood acute lymphoblastic leukemia

作　　者：朱秀娟[1,2] 贺湘玲[1,2] 伍艳鹏[1,2] 邹润英[1,2] 李婉丽[3] 邹惠[1,2] 游亚兰[1,2] 刘华[1,2] 田鑫[1,2] 

机构地区：[1]湖南师范大学第一附属医院 [2]湖南省人民医院儿科,湖南长沙410005 [3]湖南省儿童医院血液内科,湖南长沙410005

出　　处：《中国当代儿科杂志》2015年第1期11-14,共4页Chinese Journal of Contemporary Pediatrics

摘　　要：目的：探讨不同胸苷酸合成酶（TS）基因型对急性淋巴细胞白血病（ALL）患儿经大剂量甲氨蝶呤（HD-MTX）治疗后不良反应的影响。方法选取2011年3月至2013年3月确诊的ALL患儿73例，提取其基因组DNA，PCR扩增后测序鉴定TS基因型。观察并记录所有ALL患儿经HD-MTX化疗后的不良反应，并监测化疗后42-48 h MTX血药浓度。结果73例ALL患儿接受HD-MTX治疗后，其不良反应主要包括中性粒细胞减少、血红蛋白降低、血小板减少、肝脏毒性、黏膜损害和胃肠道反应，不同TS基因型患儿化疗后不良反应发生率比较差异均无统计学意义，各基因型与ALL患儿化疗后42-48 h MTX血药浓度的变化无关联。结论 TS基因多态性对ALL患儿HD-MTX化疗后不良反应的发生无影响。Objective To investigate the inlfuence of thymidylate synthase （TS） gene polymorphisms on high-dose methotrexate （HD-MTX）-related toxicities in childhood acute lymphoblastic leukemia （ALL）. Methods A total of 73 children who were diagnosed with ALL between March 2011 and March 2013 were included into this study. Genomic DNAs were extracted from their peripheral blood. And then the genotypes of TS 5＇-UTR were determined by direct DNA sequencing after PCR. The toxicity response of 73 patients receiving HD-MTX chemotherapy were observed and recorded, and plasma MTX concentrations at 42-48 hours after chemotherapy were measured. Results The main HD-MTX-related toxicities of 73 patients receiving HD-MTX chemotherapy were neutropenia, decreased hemoglobin level, thrombocytopenia, liver toxicity, mucosal damage, and gastrointestinal reactions. There were no signiifcant differences in the incidence rate of HD-MTX-related toxicities between children with different TS 5＇-UTR genotypes after chemotherapy （P〈0.05）. TS 5＇-UTR genotype was not signiifcantly correlated with plasma MTX concentrations at 42-48 hours after chemotherapy （P〈0.05）. Conclusions TS gene polymorphisms have no inlfuence on the incidence of HD-MTX-related toxicities in childhood ALL.

关 键 词：胸苷酸合成酶 基因多态性 甲氨蝶呤 不良反应 儿童 

分 类 号：R733.71[医药卫生—肿瘤]