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6 MMP, TPMT Phenotyping, 6-Mercaptopurine, 6-Thioguanine, 6-Methylmercaptopurine, Thiopurine Methyltransferase


Azathioprine (AZA, Imuran) and 6-mercaptopurine, drugs in the thiopurine family, are used to treat certain forms of leukemia, to control the immune response in inflammatory bowel diseases (Crohn’s disease, ulcerative colitis), certain autoimmune diseases (severe rheumatoid arthritis) or in combination following a kidney transplant. The proper functioning of these drugs depends on the quantity of an enzyme (protein), TPMT, whose activity is genetically programmed. About 10% of individuals carry a defective copy of the TPMT gene (heterozygous with reduced activity) while 1/300 carry both copies of the defective gene (homozygous) and zero activity of the enzyme. Low activity leads to the build-up of a by-product (6-thioguanine, 6TG) that is toxic to bone marrow. More rarely, individuals have too much enzyme activity and will not respond to normal doses of the drug.

There are different ways to assess TPMT activity, either through phenotyping or by measuring blood levels of the inactive metabolite 6-methylmercaptopurine (6-MMP) and the toxic metabolite 6-thioguanine (6TG). In the treatment of inflammatory bowel diseases, 6TG levels above 750 can be associated with toxic effects on the marrow while 6-MMP levels above 6600 can be associated with toxic effects on the liver.

Term of the Week

Hot zone

A hot zone is a section of a facility (sometimes an entire facility or even a city district) where there is a high risk of contamination by patients with an infectious disease. All individuals entering a hot zone must respect appropriate protective measures. By analogy, “cold zone” and “warm zone” are used to refer to areas where there is no infected individual or only individuals suspected of having an infection.