What is Pharmacogenomics?

Mercaptopurine belongs to a class of medicines called thiopurines. It is broken down in the body by several proteins(opens in new window), some of which convert mercaptopurine to active molecules that help kill cancer cells. Mercaptopurine is also broken down by a protein called TPMT, encoded for by the TPMT gene.

When mercaptopurine is broken down by TMPT, it is inactivated. This inactivation prevents dangerous concentrations of active molecules from building up. Changes in the TPMT gene, such as the haplotypes(opens in new window) *2, *3A or *3C, can reduce or stop the inactivation of mercaptopurine by the TPMT protein. This causes too many active molecules to build up in the body and can lead to a severe decrease in immune system activity, known as myelosuppression. Myelosuppression can be fatal.

Testing for TPMT variants(opens in new window) is widely available: the Genetic Testing Registry(opens in new window) provides over 20 laboratories that currently offer this test. In Europe, testing prior to administration of thiopurines is becoming routine clinical practice – a survey in the United Kingdom found that 67% of clinicians ordered a TPMT test before prescribing azathioprine, another drug that is broken down by TPMT.

In the United Kingdom, testing for TPMT status is mandatory for children and young adults prior to treatment on the ALL2011 trial protocol(opens in new window), and the British Association of Dermatologists' guidelines for the safe and effective prescribing of azathioprine states that TPMT activity should be checked in all patients prior to receiving azathioprine(opens in new window). The Clinical Pharmacogenetics Implementation Consortium (CPIC) has also provided dosing guidance(opens in new window) based on TPMT genotype for thiopurines.