Thiopurine methyltransferase (TPMT) and medicines



When you take a medicine (drug), your body has to have a way to handle the medicine. One way is for enzymes to metabolize (break down) the medicine. An enzyme called thiopurine methyltransferase (TPMT) has the ability to break down a class of medicines called thiopurines. Thiopurines include azathioprine (Imuran®), mercaptopurine (6-MP, Purinethol®), and thioguanine (6-TG, Tabloid®).

The thiopurines mercaptopurine and thioguanine are important chemotherapy agents used for the treatment of leukemia. Azathioprine is a medicine used to treat a variety of autoimmune diseases. Like many medicines, how well they work and their side effects can be different from person to person.

Most people have no problem breaking down thiopurines. However, a small percentage of people (about 1 in 400) have almost no ability to break down these medicines. People with no TPMT enzyme activity can have very serious side effects (infection, anemia, and bleeding) if they receive normal doses of thiopurine medicines. For these people, toxic levels of the medicine build up in the body and make blood counts too low.

Pharmacogenetic testing

DNA is like a set of instructions for your body that can help decide how well your enzymes will work. Each person differs from another at the DNA (gene) level. This means that each person has small differences in the genes that code for enzymes. The part of DNA that instructs how well TPMT enzymes will work is called the TPMT gene. The study of how genes like TPMT affect the way you break down medicines is called pharmacogenetics (FAR mah coh je NEH tiks).

Differences in your DNA that make up the TPMT gene can change how well you are able to break down thiopurine medicines (such as 6-MP, 6-TG, or azathioprine). By testing your DNA (with a pharmacogenetic test), we may find differences that can allow us to predict how well your TPMT enzyme will work. The results of this test will guide your doctor to choose the correct dose of medicine to give you if you need to take a thiopurine. The results of your TPMT pharmacogenetic test will place you into one of three groups:

  • Normal metabolizers – This means there are two copies of the normal function TPMT gene. This results in normal TPMT activity. About 9 out of 10 people have this gene status, so the “average” dose of thiopurines is the normal dose for these patients.
  • Intermediate metabolizers – This means there is one normal function gene and one copy of a non-functional TPMT gene. These patients have medium TPMT activity and may require lower doses of thiopurine medicines to avoid side effects. About 1 in 10 people have this gene status.
  • Poor metabolizers – This means there are two copies of the non-functional TPMT gene, and there is no normal TPMT enzyme. These patients are at a very high risk for having side effects (very low blood counts that could result in life-threatening problems) from 6-MP or 6-TG or azathioprine. Patients should receive much lower doses than normal to avoid side effects of low blood counts. About 1 in 400 people have this very high risk gene status.

For details about TPMT and thiopurines, please go to or


If you have questions or concerns about pharmacogenetic testing at St. Jude, call one of the Pharmaceutical Sciences research nurses at 901-595-2482 or email If you are calling from outside the Memphis area, dial toll-free 1-866-2ST-JUDE (1-866-278-5833), then dial extension 2482.


This document is not intended to take the place of the care and attention of your personal physician or other professional medical services. Our aim is to promote active participation in your care and treatment by providing information and education. Questions about individual health concerns or specific treatment options should be discussed with your physician.

St. Jude complies with health care-related federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex.

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