MTHFR、TYMS基因多态性对大剂量甲氨蝶呤化疗毒性影响的研究进展  

Research progress on the effect of MTHFR and TYMS gene polymorphisms on the toxicity of high-dose methotrexate chemotherapy

作　　者：李永乐 杨立莹 于冬旭 杨东光[1] LI Yongle;YANG Liying;YU Dongxu;YANG Dongguang(Dapartment of Hematology,the First Affiliated Hospital of Harbin Medical University,Heilongjiang Harbin 150000,China;Department of Infectious Disease,the Secend Hospital of Tianjin Medical University,Tianjin 300000,China)

机构地区：[1]哈尔滨医科大学附属第一医院血液内科,黑龙江哈尔滨150000 [2]天津医科大学第二医院感染科,天津300000

出　　处：《现代肿瘤医学》2025年第6期1057-1061,共5页Journal of Modern Oncology

摘　　要：甲氨蝶呤(methotrexate,MTX)现已成为儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)巩固和维持治疗的重要药物。大剂量甲氨蝶呤具有良好的治疗效果,但同时也带来了严重的毒性,如肝毒性、肾毒性、骨髓抑制及黏膜损害等,这些毒性往往是患者放弃治疗的诱因,也是导致患者复发率及死亡率升高的主要原因之一。有证据表明,甲氨蝶呤的毒性可能是受到甲氨蝶呤相关转运体及相关代谢酶的基因多态性的影响。该文主要对甲氨蝶呤相关代谢酶中的亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)和胸苷酸合成酶(thymidylate synthase,TYMS)的基因多态性对急性淋巴细胞白血病患儿大剂量甲氨蝶呤毒性影响的研究进展作一综述。Now,methotrexate(MTX)has become an important medicine of the consolidation and maintenance treatment of childhood acute lymphoblastic leukemia(ALL).High-dose methotrexate has a good therapeutic effect,but it also brings serious toxicity,such as liver toxicity,nephrotoxicity,bone marrow suppression,and mucosal damage.These toxicities are often the incentives for patients to give up treatment,and they are also one of the main reasons for the increase in recurrence and mortality of patients.There is evidence that the toxicity of methotrexate may be affected by genetic polymorphisms of methotrexate-related transporters and related metabolic enzymes.This paper mainly reviews the research progress on the effects of gene polymorphisms of methylenetetrahydrofolate reductase(MTHFR)and thymidylate synthase(TYMS)in methotrexate related metabolic enzymes on the toxicity of high-dose methotrexate in children with acute lymphoblastic leukemia.

关 键 词：急性淋巴细胞白血病 大剂量甲氨蝶呤 MTHFR TYMS 毒性 

分 类 号：R730.5[医药卫生—肿瘤]