贵州地区急性淋巴细胞白血病儿童TPMT、NUDT15基因多态性与6-MP耐受性分析  

Anlylisis of the polymorphisms of TPMT and NUDT15 genes in acute lymphoblastic leukemia children in Guizhou

作　　者：王彩丽[1] 方常莹 Wang Caili;Fang Changying(Department of Hematology,Guiyang City Maternal and Child Health Care Hospital,Guiyang 550002,Guizhou,China)

机构地区：[1]贵阳市妇幼保健院/儿童医院血液科,贵州贵阳550002

出　　处：《贵州医药》2024年第1期27-29,共3页Guizhou Medical Journal

摘　　要：目的观察贵州地区ALL儿童TPMT、NUDT15基因多态性,探讨其与6-MP耐受性的关系。方法收集贵阳市儿童医院血液科住院的贵州地区ALL儿童。Sanger法检测患者NUDT15c.415C>T和TPMT*2、TPMT*3A、TPMT*3B、TPMT*3C基因型。所有ALL儿童均按CCLG-2008方案化疗,每周1次监测血常规及肝肾功能。根据2016新编WHO化疗药物毒性反应分度标准,出现Ⅲ~Ⅳ度与6-MP相关的毒性反应,称为6-MP不耐受(除外感染、其他药物影响)。分析TPMT、NUDT15基因多态性与6-MP不耐受的相关性。结果共纳入患者60例,检测到TPMT突变(中间代谢型)3例(5%),正常代谢型57例(95%)。NUDT15基因CT型12例(20%),TT型1例(1.7%),CC型(野生型)47例(78.3%)。NUDT15基因突变率21.7%(13/60)显著高于TPMT基因突变率5%(3/60),差异有统计学意义(P=0.007)。TPMT突变型3例均发生6-MP不耐受(100%),NUDT15突变型13例中11例发生6-MP不耐受(84.6%)。结论TPMT、NUDT15基因突变与6-MP不耐受相关(P<0.05),联合检测TPMT、NUDT15基因对调整6-MP使用,减少6-MP不良反应提供依据。Objective To observe the polymorphisms of TPMT and NUDT15 genes in acute lymphoblastic leukemia(ALL)children in Guizhou,and explore the relationship between them and 6-MP tolerance.Methods ALL children from Guizhou area who were hospitalized in Guiyang Children’s Hospital were collected.NUDT15c.415C>T and TPMT*2,TPMT*3A,TPMT*3B and TPMT*3C genotypes were detected by Sanger method.ALL children with ALL were treated with chemotherapy according to CCLG-2008 regimen,and blood routine and liver and kidney function were monitored once a week.According to the newly compiled WHO Toxicity rating standard of chemotherapy drugs in 2016,there were III-IV toxic reactions associated with 6-MP,which was called 6-MP intolerance(except infection and other drug effects).The correlation between TPMT and NUDT15 gene polymorphism and 6-MP intolerance was analyzed.Results A total of 60 patients were included.TPMT mutation that intermediate metabolic type was detected in 3 cases(5%)and normal metabolic type was detected in 57 cases(95%).There were 12 NUDT15 cases with CT type(20%),1 case with TT type(1.7%)and 47 cases with CC type that wild type(78.3%).NUDT15 gene mutation rate of 21.7%(13/60)was significantly higher than TPMT gene mutation rate of 5%(3/60)(P=0.007).6-MP intolerance occurred in 3 cases of TPMT mutant(100%),and in 11 cases of 13 NUDT15 mutant(84.6%).Conclusion The mutations of TPMT and NUDT15 genes are correlated with 6-MP intolerance(P<0.05),and the combined detection of TPMT and NUDT15 genes can provide evidence for regulating the use of 6-MP and reducing the adverse effects of 6-MP.

关 键 词：6-MP TPMT NUDT15 基因多态性 贵州地区 急性淋巴细胞白血病 儿童 

分 类 号：R733.71[医药卫生—肿瘤]