TPMT and NUDT15 and Medicines

When you take a medicine, your body needs a way to handle it. One way is for enzymes to metabolize (break down) the medicine. Two enzymes break down a class of medicines called thiopurines: thiopurine methyltransferase (TPMT) and nudix-type motif 15 (NUDT15). Thiopurines include mercaptopurine (6-MP, Purinethol®), thioguanine (6-TG, Tabloid®), and azathioprine (Imuran®).  

Thiopurine medicines 

Mercaptopurine and thioguanine are important chemotherapy medicines used to treat leukemia. Azathioprine is a medicine used to treat some autoimmune diseases. Like many medicines, how well thiopurines work and their side effects can be different from person to person. 

TPMT and NUDT15 function 

Most people have no problem breaking down thiopurine medicines. However, a small number of people have almost no ability to break down these medicines. For these people, toxic levels of the medicine build up in the body. People with no TPMT or NUDT15 enzyme function can have very serious side effects such as low blood counts and infection, if they receive normal doses of thiopurine medicines.   

Pharmacogenomic testing 

Each person differs from another at the DNA level. Genes are segments of DNA that act as a set of instructions and tell the body how to work. The TPMT and NUDT15 genes are sections of DNA that instruct how well the enzymes will work.

The study of how genes like TPMT and NUDT15 affect the way your body interacts with medicines is called pharmacogenomics. Differences in your DNA that make up the TPMT or NUDT15 gene can change how well you are able to break down thiopurine medicines such as mercaptopurine, thioguanine, or azathioprine.  

A pharmacogenomic test looks for differences that can help your medical team know how well your TPMT and NUDT15 enzymes will work. The test results can help your doctor and pharmacist choose the correct dose of medicine to give you.  

Gene groups 

The results of your TPMT and NUDT15 pharmacogenomic test will place you into one of three groups: 

Normal metabolizer – People in this group have normal TPMT function (TPMT normal metabolizer) and normal or less active NUDT15 enzyme function (NUDT15 normal metabolizer or intermediate metabolizer). Most people are in this group. About 90 in 100 people are this group.  

Intermediate metabolizer – People in this group have slightly reduced TPMT function (TPMT intermediate metabolizer) along with normal or less active NUDT15 enzyme function (NUDT15 normal metabolizer or intermediate metabolizer). They may need lower doses of thiopurine medicines to avoid side effects. About 10 in 100 people are in this group. 

Poor metabolizer – People in this group have no TPMT enzyme function (TPMT poor metabolizer) or no NUDT15 enzyme function (NUDT15 poor metabolizer). These patients are at high risk for having side effects with thiopurines, including very low blood counts that could be life-threatening. These patients should receive much lower than normal doses of mercaptopurine, thioguanine, or azathioprine. About 5 in 1000 people are in this group. 

After the first dose, the dose of thiopurine may change based on blood counts. 

Scientists continue to find new information about which medicines are affected by gene test results. Talk to your doctor or pharmacist if you have questions about your medicines, side effects, or pharmacogenomic testing.  

Find more information about genes that are being used to make medication therapy decisions for patients at St. Jude.   

If you have questions about pharmacogenomic testing done at St. Jude, you can email the Clinical Pharmacogenomics Program at pharmacogenomics@stjude.org.