NUDT15 c.415C>T和TPMT*3C基因多态性与儿童急性淋巴细胞白血病诱导期6-巯基嘌呤耐受性相关性研究  

The correlation between NUDT15 c.415C>T and TPMT*3C gene polymorphisms and 6-MP tolerance during induction chemotherapy in children with acute lymphoblastic leukemia

作　　者：杜成成 韩蕊 王媛 孔庆玲 王楠 刘璐 王岩 王磊 徐淑梅 安琪 DU Chengcheng;HAN Rui;WANG Yuan;KONG Qingling;WANG Nan;LIU Lu;WANG Yan;WANG Lei;XU Shumei;AN Qi(Department of Hematologic Oncology,Xuzhou Children's Hospital Affiliated to Xuzhou Medical University,Xuzhou,Jiangsu 221002,China)

机构地区：[1]徐州医科大学附属徐州儿童医院血液肿瘤内科,江苏徐州221002

出　　处：《安徽医药》2025年第3期591-595,共5页Anhui Medical and Pharmaceutical Journal

摘　　要：目的探讨核苷二磷酸连接的X成份型基元15(NUDT15)c.415C>T rs116855232和硫嘌呤甲基转移酶(TPMT)*3C rs1142345基因多态性与儿童急性淋巴细胞白血病(ALL)病儿6-巯基嘌呤(6-MP)耐受性的关系。方法选取2019年9月至2022年11月在徐州市儿童医院确诊54例ALL病儿为研究对象,所有病儿均进行TPMT*3C和NUDT15 c.415C>T多态性的基因分型。结合临床资料,分析TPMT和NUDT15基因多态性对儿童ALL诱导期治疗中6-MP耐受性的影响。结果54例病儿中B细胞(B)-ALL 47例(87.04%)、T细胞(T)-ALL 7例(12.96%)。通过限制性片段长度多态性聚合酶链反应(PCR-RFLP)确定的基因型分布为:NUDT15 rs116855232位点包括CC野生型45例(83.3%),CT杂合型7例(13.0%),TT纯合型2例(3.7%),等位基因变异频率为10.2%;TPMT*3C rs1142345位点包括AA野生型51例(94.4%),AG杂合型3例(5.6%),等位基因变异频率为2.8%。NUDT15 rs116855232突变组(CT+TT型)白细胞计数<1×10^(9)/L的持续时间长于野生型组(CC型)(P=0.001);突变型组血小板的输注量10(0,20)U多于野生组0(0,10)U(P=0.022);突变型组中性粒细胞绝对计数<0.5×10^(9)/L的持续时间9(4,17)d长于野生型组6(3,9)d(P=0.036)。结论NUDT15 rs116855232基因多态性可以影响儿童ALL病儿对6-MP的耐受性。在有条件的情况下,对病儿进行治疗前的NUDT15基因型检测,优化6-MP使用剂量,有助于减少严重骨髓抑制持续时间和血液制品输注量。Objective To explore the correlation between nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)c.415C>T rs116855232 and thiopurine methyltransferase(TPMT)*3C rs1142345 gene polymorphisms with 6-mercaptopurine(6-MP)tolerance in children with childhood acute lymphoblastic leukemia(ALL).Methods A total of 54 children with ALL diagnosed in Xuzhou Children's Hospital from September 2019 to November 2022 were selected as the research objects,all of whom were genotyped by TPMT*3C and NUDT15 c.415C>T polymorphisms.In combination with clinical data,the effects of TPMT and NUDT15 gene polymorphisms on the tolerance of 6-MP during induction chemotherapy for childhood ALL were analyzed.Results Among the 54 children,47(87.04%)children had B-cell(B)-ALL and 7(12.96%)children had T-cell(T)-ALL.Genotype distribution was determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The counts of CC,CT and TT genotypes for NUDT15 rs116855232 were 45(83.3%),7(13.0%)and 2(3.7%),respectively.The frequency of allelic variation was 10.2%for NUDT15 rs116855232.The counts of AA and AG genotypes for TPMT*3C rs1142345 were 51(94.4%)and 3(5.6%),respectively.The frequency of allelic variation was 2.8%for TPMT*3C rs1142345.The NUDT15 rs116855232 mutant group(CT+TT genotype)exhibited a significantly longer duration of WBC count<1×10^(9)/L compared with the wild-type group(CC genotype)(P=0.001).The median platelet infusion amount was higher in the mutant group than in the wild-type group[10(0,20)U vs.0(0,10)U](P=0.022).Additionally,the median duration of absolute neutrophil count<0.5×10^(9)/L was longer in the mutant group compared to the wild-type group[9(4,17)d vs.6(3,9)d](P=0.036).Conclusions NUDT15 rs116855232 gene polymorphism can influence the tolerance of 6-MP in the treatment of childhood ALL.If allowed,NUDT15 genotype identification is done before treatment in order to optimize the dose of 6-MP,which helps to shorten severe myelosuppression and lower the volume of blood product infusion.

关 键 词：急性淋巴细胞白血病 核苷二磷酸 X成份型基元15 硫嘌呤甲基转移酶 基因多态性 6-巯基嘌呤 儿童 

分 类 号：R733.71[医药卫生—肿瘤]