TPMT and NUDT15 Testing — Before You Start Thiopurines

If you carry a poor-function variant in TPMT or NUDT15 and receive a thiopurine without that being known, active drug metabolites can build up to levels the bone marrow cannot tolerate. The result is severe myelosuppression — a dangerous fall in white cells, red cells, and platelets — which can lead to serious infection or bleeding. This is a predictable and potentially preventable event, which is why CPIC and ASCO guidance addresses testing before starting. If you are already on the drug and testing has not been done, tell your oncologist so they can decide whether to test now and how closely to watch your counts.

CPIC recommends TPMT and NUDT15 testing for anyone being considered for a thiopurine drug — 6-mercaptopurine, azathioprine, or thioguanine. In oncology, these drugs are used most commonly in maintenance therapy for acute lymphoblastic leukaemia, but azathioprine also appears in some lymphoma and autoimmune protocols. The recommendation applies regardless of ancestry, though the variant most likely to be found differs by population. Your oncologist will determine whether testing is appropriate in your specific situation and what can be arranged from your treating centre.

Not necessarily, particularly for patients of South or East Asian ancestry. TPMT and NUDT15 are separate genes encoding different enzymes, and a result for one says nothing about the other. Because NUDT15 variants are substantially more common in Indian and other Asian patients, a normal TPMT result while NUDT15 is untested leaves a meaningful gap in the safety information your oncologist has before prescribing. Ask specifically whether both genes have been checked, not just one.

Testing for both genes is available at some specialist pharmacogenomics laboratories and larger cancer centres in India, though it is not uniformly available at every centre. Some samples need to be sent to a reference laboratory, which adds days to the turnaround. Availability is increasing as pharmacogenomic testing becomes more integrated into oncology practice. Your oncologist is the right person to find out what is accessible from your treating centre, how the sample gets there, and how long the result will take.

A variant result does not automatically mean you cannot receive a thiopurine. It means your oncologist has information they need to plan treatment and monitoring appropriately. What they decide depends on which variant you carry, what it predicts about your enzyme function, which drug is being considered, and the clinical context. The decision is your oncologist's to make, with the test result as one input. Do not delay starting treatment or refuse a prescribed drug because of a result before talking to your team.

A standard blood draw — the same kind used for routine blood tests. The sample is sent to a laboratory where your DNA is analysed for known variants in the TPMT and NUDT15 genes. The result classifies your predicted enzyme activity based on the variants found. It needs to be done only once, as your genetic makeup does not change. The result is then interpreted by your oncologist alongside your diagnosis, the drug being considered, and your overall clinical picture.

Turnaround time varies by laboratory. At centres where testing is done in-house, results may be available within a few days. If the sample must be sent to a reference laboratory, it typically takes longer. Ask your team when the sample was dispatched and when the result is expected, so there is a clear timeline before your planned treatment start date. If your treatment is urgent and a result is not yet available, your oncologist will make a clinical judgement about timing and monitoring in the interim.

In oncology, 6-mercaptopurine is used most commonly as part of maintenance therapy for acute lymphoblastic leukaemia, particularly in children and young adults. Azathioprine appears in some lymphoma protocols and in autoimmune conditions that can overlap with cancer care. Thioguanine is used in certain leukaemia regimens. These drugs are taken by mouth and are typically part of a prolonged course rather than short-cycle chemotherapy. Your oncologist will explain which drug applies to your diagnosis and the role it plays in your specific treatment plan.