TPMT基因多态性与儿童ALL的6-MP个体化治疗

TPMT gene polymorphism and 6-MP dividual therapy in children ALL

6-巯基嘌呤(6-MP)是儿童急性淋巴细胞白血病(ALL)维持治疗阶段的关键化疗药物。巯嘌呤甲基转移酶(TPMT)作为巯嘌呤类药物在体内代谢过程中的关键酶之一,其基因多态性及酶活性与急性淋巴细胞白血病患儿对6-巯基嘌呤的剂量耐受性有一定的相关性,从而进一步影响急性淋巴细胞白血病患儿服用6-巯基嘌呤后不良反应的发生程度和远期预后。此外,巯嘌呤甲基转移酶基因型也可能与继发恶性肿瘤有关。因此,检测巯嘌呤甲基转移酶活性或基因型,有助于预测巯嘌呤类药物不良反应的严重程度,及时调整给药剂量,制订安全合理的个体化用药方案。

6-mercaptopurine（6-MP） is a key drug for the maintainable treatment in childhood acute lymphoblastie leukemia（ALL）.Thiopurine S-methyhransferase （TPMT） has been confirmed as one of the most distinctive enzymes,its gene polymorphisms and activity are associated with tolerance in ALL children which further affect the incidence of adverse reactions and long-term prognosis of ALL children with 6-MP.In addition, TPMT genotype may also be related to second malignant neoplasm（SMN）.So detecting TPMT genotypes may be helpful to predict the severity of adverse reaction with thiopurine drugs, adjustment of the dosage in time, might make a safety and reasonable dividual medicine programs in clinical treatment. This article reviewed the effect of TPMT gene polymorphism on the individual treatment of 6 - MP in childhood ALL.