The Clinical Impact of Thiopurine Methyltransferase Polymorphisms on Thiopurine Treatment
Nucleosides, Nucleotides and Nucleic Acids, 2004Acute lymphoblastic leukaemia (ALL) is the most common malignancy of childhood. Although current treatment results in long term survival in over 70% of cases there is evidence that as many as 50% could have been cured using a less complex regimen with a lower incidence of long term side effects.
S A, Coulthard +3 more
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Pharmacogenetics of Thiopurine S-Methyltransferase and Thiopurine Therapy
Therapeutic Drug Monitoring, 2004Most medications exhibit wide interpatient variability in their efficacy and toxicity. For many medications, these interindividual differences result in part from polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and/or drug targets (eg, receptors, enzymes).
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Interethnic difference in thiopurine methyltransferase activity
Clinical Pharmacology and Therapeutics, 1992A number of metabolic pathways are subject to both genetic polymorphism and interethnic differences. A catabolic pathway of 6-mercaptopurine, red blood cell (RBC) thiopurine methyltransferase (TPMT) activity showed genetic polymorphism in Caucasians, but variation according to ethnicity has not been studied. We investigated if red blood cell thiopurine
B, Klemetsdal +7 more
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Thiopurine methyltransferase in acute lymphoblastic leukemia
Blood, 2006We recently reported that specific genetic polymorphisms, particularly polymorphisms in thymidylate synthase (TYMS) and glutathione S -transferase M1 (GSTM1) predicted the risk of relapse among children with acute lymphoblastic leukemia (ALL).[1][1] An accompanying commentary noted surprise that ...
Mary V, Relling +3 more
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Individualization of Thiopurine Therapy: Thiopurine S -Methyltransferase and Beyond
Pharmacogenomics, 2009The metabolism of a given drug depends, not solely on a particular enzyme, but rather on a complex metabolic network. Thiopurine S-methyltransferase (TPMT) catalyzes the methylation, and thus deactivation, of 6-mercaptopurine, a thiopurine used in the treatment of acute lymphoblastic leukemia.
Natasa, Karas-Kuzelicki +1 more
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Clinical Pharmacogenomics of Thiopurine S-methyltransferase
Current Clinical Pharmacology, 2006Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP), thioguanine and azathioprine (AZA). These drugs are used to treat conditions such as acute lymphoblastic leukemia, inflammatory bowel disease, rheumatoid arthritis, and organ transplant rejection. This review highlights the polymorphisms
Zhou, Shufeng, Brink
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The Effect of Thiopurine Methyltransferase Expression on Sensitivity to Thiopurine Drugs
Molecular Pharmacology, 2002Although the thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well established agents for the treatment of leukemia, controversies remain regarding their main mode of action. Previous evidence has suggested that although 6-TG exerts a cytotoxic effect through incorporation of 6-thioguanine nucleotides into newly synthesized DNA ...
Coulthard +13 more
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Human thiopurine methyltransferase pharmacogenetics: Gene sequence polymorphisms*
Clinical Pharmacology & Therapeutics, 1997Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs. TPMT activity is regulated by a common genetic polymorphism that is associated with large individual variations in thiopurine toxicity and efficacy. We previously cloned the functional gene for human TPMT and reported a common variant allele for low enzyme activity ...
D, Otterness +10 more
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Clinical Utility of Thiopurine S-Methyltransferase Genotyping
American Journal of PharmacoGenomics, 2004Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that plays a major role in the metabolism of thiopurine drugs such as mercaptopurine and azathioprine. The interindividual differences in response to thiopurine administration is in part due to the presence of genetic polymorphisms in the gene that regulates TPMT activity.
Hèctor, Corominas, Montserrat, Baiget
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Pharmacogenomics: Catechol O-Methyltransferase to Thiopurine S-Methyltransferase
Cellular and Molecular Neurobiology, 20061. Pharmacogenomics is the study of the role of inheritance in variation in the drug response phenotype-a phenotype that can vary from adverse drug reactions at one end of the spectrum to lack of therapeutic efficacy at the other. 2. The thiopurine S-methyltransferase (TPMT) genetic polymorphism represents one of the best characterized and most ...
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