The thiopurines: An update

被引：99

作者：

Coulthard, S ^{[1
]}

Hogarth, L ^{[1
]}

机构：

[1] Newcastle Univ, No Inst Canc Res, Leukaemia Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

来源：

INVESTIGATIONAL NEW DRUGS | 2005年 / 23卷 / 06期

关键词：

thiopurine methyltransferase; 6-mercaptopurine; 6-thioguanine; azathioprine; leukaemia;

D O I：

10.1007/s10637-005-4020-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The thiopurine drugs, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) are commonly used cytotoxic agents. A derivative of 6-MP, azathioprine, is commonly used as an immunosuppressant. A prominent route for the metabolism of these agents is mediated by the enzyme thiopurine methyltransferase (TPMT). This enzyme exhibits considerable inter-individual variation in activity, partly due to the presence of common genetic polymorphisms, which influence cytotoxicity of the thiopurine drugs. Variations in the number of tandem repeats in the 5' promoter region have also been shown to influence TPMT expression in vitro. In this article, we review the impact of variations in TPMT activity on sensitivity to the thiopurine drugs in vitro and also in vivo in terms of their clinical efficacy and toxicity. A possible relationship between TPMT and secondary malignancies is also reviewed.

引用

页码：523 / 532

页数：10

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