6-巯基嘌呤治疗儿童急性淋巴细胞白血病个体化用药的研究进展

发布时间：2018-02-27 21:08

本文关键词： -巯基嘌呤急性淋巴细胞白血病个体化用药基因组学代谢酶转运体　出处：《中国药房》2017年20期 　论文类型：期刊论文

【摘要】：目的:了解6-巯基嘌呤(6-MP)治疗急性淋巴细胞白血病(ALL)个体化用药的研究进展,以期为6-MP治疗ALL个体化用药提供依据。方法:查阅近年来国内外相关文献,就6-MP治疗ALL时与代谢有关的代谢酶基因的多态性和转运体酶基因的多态性的研究进行归纳和总结。结果:6-MP代谢酶和转运体酶的基因多态性是影响6-MP个体化治疗ALL患儿疗效和不良反应的重要因素。其中,代谢酶基因硫嘌呤甲基转移酶、亚甲基四氢叶酸还原酶、重组人肌苷三磷酸酶和转运体酶基因多药耐药相关蛋白5的多态性影响6-MP个体化治疗的疗效和不良反应;转运体基因多药耐药1、溶质运载蛋白(SLC)28A3和SLC29A2的多态性仅在体外研究中显示出对6-MP转运和耐药性等的影响。结论:关于6-MP治疗ALL的代谢和转运的相关基因多态性的研究尚存在样本量偏小、研究群体局限于某一种族、转运体相关基因多态性的研究不够充分和药物受体基因多态性的研究匮乏等不足,有待将与6-MP相关的代谢酶、转运体和受体的单核苷酸多态性进行扩大样本量的综合研究,归纳出给药剂量的综合预测方程,以为6-MP在临床的个体化给药提供参考。
[Abstract]:Objective: to investigate the research progress of 6-mercaptopurine (6-MPP) in the treatment of acute lymphoblastic leukemia (ALL) in order to provide the basis for the individualized use of 6-MP in the treatment of ALL. Methods: to review the relevant literature at home and abroad in recent years. The polymorphism of metabolic enzyme gene and transporter gene in 6-MP treatment of ALL were summarized and summarized. Results the gene polymorphism of 6-MP metabolizing enzyme and transporter enzyme was the influence of 6-MP individualized therapy on ALL. The important factors of curative effect and adverse reaction in children. The polymorphisms of thiopurine methyltransferase, methylenetetrahydrofolate reductase, recombinant human inosine triphosphatase and transporter gene multidrug resistance-associated protein 5 affect the efficacy and adverse effects of 6-MP individualized therapy. The polymorphisms of transporter gene multidrug resistance (MDR), solute transporter protein (SMP) SLC328A3 and SLC29A2 only showed the effect on the transport and drug resistance of 6-MP in vitro. Conclusion: the polymorphism of 6-MP gene in the treatment of ALL is related to the gene polymorphisms in metabolism and transport. There is still a small sample size in the study. The study population is limited to a certain race, the study of transporter related gene polymorphism is insufficient, and the study of drug receptor gene polymorphism is insufficient, so that the metabolic enzymes associated with 6-MP are needed. The single nucleotide polymorphisms of transporters and receptors were studied to enlarge the sample size, and the comprehensive prediction equation of drug dosage was concluded, which provided a reference for the individualized administration of 6-MP in clinic.
【作者单位】：青岛大学附属医院药学部;
【分类号】：R733.71

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