NUDT15基因多态性与儿童急性淋巴细胞白血病6-巯基嘌呤治疗耐受性的关系  

Relationship between NUDT15 gene polymorphism and tolerance to treatment with 6-mercaptopurine in children with acute lymphoblastic leukemia

作　　者：王静[1] 王晓欢[1] 郝国平[1] 程艳丽[1] 陆海燕[1] 索涛莉 Wang Jing;Wang Xiaohuan;Hao Guoping;Cheng Yanli;Lu Haiyan;Suo Taoli(Department of Hematology,Jinyuan Branch,Shanxi Children's Hospital,Taiyuan 030025,China)

机构地区：[1]山西省儿童医院晋源院区血液科,太原030025

出　　处：《白血病．淋巴瘤》2022年第5期286-289,共4页Journal of Leukemia & Lymphoma

基　　金：山西省卫生健康委员会科研课题(2018072)。

摘　　要：目的探讨儿童急性淋巴细胞白血病(ALL)患者NUDT15基因多态性与6-巯基嘌呤(6-MP)治疗耐受性的关系。方法选择2019年1月至2020年12月于山西省儿童医院明确诊断为ALL的患儿58例,均采用CCLG-ALL2018方案化疗,骨髓达完全缓解,在维持治疗阶段接受6-MP口服治疗。采用实时荧光定量聚合酶链反应检测NUDT15基因单核苷酸多态性,分析不同NUDT15基因型患儿应用6-MP治疗的骨髓抑制情况及6-MP耐受剂量。结果58例患儿中,NUDT15基因TT型3例,CC型46例,TC型9例。在6-MP维持治疗阶段,3组不同NUDT15基因型患儿的白细胞计数、血红蛋白、血小板计数比较,差异均有统计学意义(均P<0.05)。58例患儿中,23例(39.66%)用药后出现不同程度的中性粒细胞减少,包括NUDT15基因CC型16例,TC型5例,TT型2例。3组间骨髓抑制情况比较,差异有统计学意义(H=29.10,P<0.05)。TT型、CC型、TC型患儿6-MP使用剂量分别为(10.4±8.8)mg·m^(-2)·d^(-1)、(41.5±1.3)mg·m^(-2)·d^(-1)、(36.7±2.4)mg·m^(-2)·d^(-1),差异有统计学意义(F=16.95,P<0.05)。结论不同NUDT15基因型患儿6-MP耐受性不同,NUDT15基因多态性与ALL患儿维持治疗期间6-MP不耐受相关,可能影响疾病的治疗。Objective To investigate the relationship between NUDT15 gene polymorphism and tolerance to treatment with 6-mercaptopurine(6-MP)in children with acute lymphoblastic leukemia(ALL).Methods Fifty-eight children diagnosed with ALL in Shanxi Children's Hospital from January 2019 to December 2020 were recruited.All of them were treated with CCLG-ALL2018 chemotherapy regimen and the bone marrow showed complete remission.They received 6-MP oral treatment during maintenance treatment.Single nucleotide polymorphism of NUDT15 gene was detected by real-time fluorescence quantitative polymerase chain reaction.The bone marrow suppression after 6-MP treatment and 6-MP tolerance dose in patients with different NUDT15 genotypes were analyzed.Results Among 58 patients,3 patients had NUDT15 TT genotype,46 patients had CC genotype and 9 patients had TC genotype.During maintenance treatment with 6-MP,the differences in leukocyte count,hemoglobin and platelet count among the three groups of patients with different NUDT15 genotypes were statistically significant(all P<0.05).Among 58 patients,23(39.66%)patients had varying degrees of neutropenia after medication,including 16 cases of NUDT15 CC genotype,5 cases of TC genotype and 2 cases of TT genotype.There was a statistically significant difference in bone marrow suppression among the three groups(H=29.10,P<0.05).The dosages of 6-MP used in patients with TT,CC and TC genotypes were(10.4±8.8)mg·m^(-2)·d^(-1),(41.5±1.3)mg·m^(-2)·d^(-1) and(36.7±2.4)mg·m^(-2)·d^(-1),respectively,and the difference was statistically significant(F=16.95,P<0.05).Conclusions Children with different NUDT15 genotypes have different tolerance to 6-MP,and NUDT15 gene polymorphism is associated with 6-MP intolerance during maintenance treatment in children with ALL,which may affect the treatment of the disease.

关 键 词：白血病 淋巴样 多态性 单核苷酸 NUDT15基因 巯基嘌呤 中性粒细胞减少 

分 类 号：R733.7[医药卫生—肿瘤]