Journal
BIOCHEMICAL PHARMACOLOGY
Volume 79, Issue 9, Pages 1211-1220Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2010.01.006
Keywords
Acute lymphoblastic leukemia; 6-Mercaptopurine; 6-Thioguanine; Azathioprine; Hypoxanthine-guanine phosphoribosyl transferase; Thiopurine methyltransferase; Inosine 5 '-monophosphate dehydrogenase; Transport; Pharmacogenetics
Categories
Funding
- Children Cancer Foundation
- Cancer and Allergy Foundation
- Cancer Society in Stockholm
- King Gustaf V jubilee Fund
- Swedish Medical Society
- Swedish Cancer foundation
- Karolinska Institute Foundations
- Swedish Research Council
- County Council of Ostergotland
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Thiopurines are the backbone of current anti-leukemia regimens and have also been effective immunosuppressive agents for the past half a century. Extensive research on their mechanism of action has been undertaken, yet many issues remain to be addressed to resolve unexplained cases of thiopurine toxicity or treatment failure. The aim of this review is to summarize current knowledge of the mechanism of thiopurine action in experimental models and put into context with clinical observations. Clear understanding of their metabolism will contribute to maximizing efficacy and minimizing toxicity by individually tailoring therapy according to the expression profile of relevant factors involved in thiopurine activation pathway. (C) 2010 Published by Elsevier Inc.
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