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TPMT and NUDT15: the two gene tests before thiopurine tablets | CION Cancer Clinics
TPMT and NUDT15 are two genes that decide how safely your body handles thiopurines, the tablets called mercaptopurine, thioguanine and azathioprine. If either gene works poorly, a normal dose can badly lower blood counts. A simple blood test before the first dose shows which starting dose is safer. This page explains what the two tests look for, why both matter in India, and what a result changes. At CION Cancer Clinics, our team helps carriers and their families plan checks, next steps and support after a genetic result.
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Medically reviewed by Dr. Naresh GunduConsultant Medical Oncologist · MBBS, DNB (Internal Medicine), DM (Medical Oncology, AIIMS) · last reviewed September 2026, next review due September 2027
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On this page
- What do the TPMT and NUDT15 tests actually check?
- What can a TPMT or NUDT15 result say?
- How does the test fit into the first weeks of treatment?
- The words on a TPMT or NUDT15 report, in plain language
- How are TPMT and NUDT15 different?
- What this page cannot tell you
- Four things families assume about these tests
- Common questions about TPMT and NUDT15 testing
The short answer
What do the TPMT and NUDT15 tests actually check?
Both tests look at genes that help your body break down thiopurine medicines. When the genes work normally, the body clears the drug at the expected rate. When one or both work poorly, more of the active drug reaches the bone marrow, and a standard dose can drop blood counts dangerously low.
What the drug does inside the body
Thiopurines are turned into active substances inside cells. Those substances stop leukaemia cells from copying their DNA, which is why the tablets are central to the long maintenance phase of childhood acute lymphoblastic leukaemia. The same substances also slow the healthy bone marrow that makes blood cells. TPMT sends part of the drug down a safer side path. NUDT15 breaks down the active form before it piles up. Lose either enzyme, and the active form builds up in the marrow.
Why the test comes before the first dose
The damage is quiet at first. Counts can look fine for a week or two and then fall sharply, sometimes with a serious infection. Testing first lets the oncologist choose a safer starting dose instead of finding the problem in a hospital bed. It also saves weeks of stopping and restarting treatment while the team works out what went wrong.
The test does not decide whether you get the drug. It decides how much you start on.Reading the result
What can a TPMT or NUDT15 result say?
Each gene is reported on its own line. The labels are the same for both, and one result can be normal while the other is not.
Normal metaboliser
Two working copies of the gene. The usual starting dose is generally used, and it is then adjusted on blood counts exactly as it would be for anyone else.
What happens next
- Standard starting dose
- Routine blood count checks
- No extra caution from this gene
Intermediate metaboliser
One working copy and one that works poorly. Guidelines suggest starting below the usual dose and raising it if counts allow. Most people in this group tolerate treatment well once the dose is right.
Poor metaboliser
Both copies work poorly or not at all. A normal dose can wipe out the blood counts. In leukaemia the drug is usually still given, at a far smaller dose or less often, with very close monitoring.
Uncertain or indeterminate
The laboratory found a variant whose effect is not yet known, or could not assign a label. Teams usually start cautiously and lean more heavily on blood counts.
Keep this report. A variant can be reclassified as evidence grows.Not sure whether this applies to you?
Ask an oncologistStep by step
How does the test fit into the first weeks of treatment?
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A blood sample, ideally before the first dose
A small blood sample is enough. The gene test reads inherited DNA, so a recent blood transfusion does not spoil it. A TPMT enzyme test, which measures activity in red cells, can be misleading after a transfusion in the previous few months.
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The laboratory reads both genes
It looks for known variants in TPMT and in NUDT15. Some laboratories still test TPMT alone. Check that NUDT15 was on the request, because in Indian families it is often the more important of the two.
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The oncologist sets a starting dose
The result is combined with the treatment protocol, body size and current blood counts. A gene result changes the starting point. It does not replace clinical judgement.
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Blood counts guide every change after that
Regular full blood counts show whether the marrow is coping. The dose moves up or down to keep the white cell count in a target range, whatever the gene result said.
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The result is kept for life
Genes do not change. The same result applies if azathioprine or thioguanine is ever prescribed later, for any reason.
On your report
The words on a TPMT or NUDT15 report, in plain language
- Thiopurine
- The family of medicines this test is about: mercaptopurine, often written 6-MP, thioguanine and azathioprine.
- Genotype
- The exact gene spelling found in your DNA. It is fixed from birth and does not change over your life.
- Phenotype
- What that spelling predicts the enzyme will do: work normally, work at reduced strength, or barely work at all.
- Star allele
- The naming system for gene versions. A report may say TPMT *1/*3C or NUDT15 *1/*3. The *1 usually means the standard version.
- Enzyme activity test
- A separate TPMT test that measures the enzyme in red blood cells. No routine equivalent exists for NUDT15.
- Myelosuppression
- Bone marrow slowing down, so fewer blood cells are made. This is the harm the test is trying to prevent.
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Side by side
How are TPMT and NUDT15 different?
TPMT
NUDT15
Known since the early years of thiopurine use
Its role was recognised far more recently
Faulty versions more common in people of European descent
Faulty versions more common in East and South Asian families
Can be tested as genotype or as enzyme activity
Tested as genotype only
A normal result does not clear NUDT15
A normal result does not clear TPMT
Being straight with you
What this page cannot tell you
It cannot tell you the right dose for you or your child. That depends on the treatment protocol, body size, blood counts and every other medicine being taken. Allopurinol, used to protect the kidneys early in leukaemia treatment, changes how mercaptopurine is handled, which is one reason the team asks about every tablet at home.
It cannot read a report you are holding
What your specific variant means is a question for the oncologist or genetic counsellor who ordered the test. Rare variants in either gene may not be on every laboratory panel, and studies of NUDT15 in Indian patients so far are small.
Who this does not apply to
Most people never take a thiopurine, and for them this test has no use. It is not a cancer screening test and says nothing about cancer risk in the family. It is only worth doing when one of these drugs is planned or already being given.
What a normal result does not promise
Low blood counts have many causes besides these two genes, including the leukaemia itself, infection and other drugs. A normal result means one known risk has been checked. Regular counts still continue.
Commonly believed
Four things families assume about these tests
"The TPMT result was normal, so the drug is safe."
TPMT is only half the picture. A child can have a normal TPMT result and a faulty NUDT15 gene, and in South Asian families that combination is not rare. Ask whether both genes were tested.
"A poor metaboliser result means my child cannot have the medicine."
In leukaemia the drug is usually too important to drop. It is given at a much smaller dose, or on fewer days of the week, and counts are watched closely. The result changes how it is given, not whether.
"The test has to be repeated before every course."
A gene result lasts a lifetime because your genes do not change. What is repeated is the blood count, which tells the team how the marrow is coping right now.
"A poor result means the leukaemia is more dangerous."
The result describes how the body handles one family of drugs. It says nothing about how aggressive the leukaemia is. It is inherited, so brothers and sisters may share it, which matters only if they ever need a thiopurine themselves.
Questions we are asked
Common questions about TPMT and NUDT15 testing
Is this a test on the leukaemia or on my child?
On your child. It reads inherited DNA from a blood sample, which is the same in every healthy cell. It is not a test of the leukaemia and does not change the diagnosis. Its only job is to predict how the body will handle thiopurine tablets.
Does my child need both tests or just one?
International guidelines recommend both genes wherever testing is available. In Indian families NUDT15 is often the more useful result, because faulty versions of it are more common here than faulty versions of TPMT. A TPMT test alone can miss the real reason a child cannot tolerate the drug.
Does treatment have to wait for the result?
Usually not. In most childhood leukaemia protocols, thiopurines start after the first phase of treatment, so there is often time for the result to return. Your oncologist will tell you whether anything needs to be held back while you wait.
Treatment has already started without the test. Is it too late?
No. The test can still be sent, and blood counts are already being used to guide the dose. If counts have fallen unusually fast or stayed low for a long time, a gene result can help explain why and settle the dose for the rest of treatment.
Do adults ever need this test?
Yes. Adults with acute lymphoblastic leukaemia take the same drugs, and azathioprine is widely used for bowel, skin and joint conditions. The result is the same whatever your age, so a test done in childhood still counts in adult life.
Should brothers and sisters be tested too?
Only if one of them ever needs a thiopurine. The result is inherited, so siblings may share it, but it carries no cancer risk and needs no action in a healthy child. Mention the family result to any doctor who prescribes one of these drugs later.
Is the test covered by Aarogyasri or insurance?
It depends on the treatment package, the laboratory and the hospital. Some leukaemia packages include it and some do not. Ask the billing desk before the sample goes, so the cost is not a surprise.
Does the result change diet or other medicines?
It does not change diet. It does matter for some other medicines, especially allopurinol, which raises thiopurine levels. Carry a copy of the result and show it to every doctor and pharmacist, including for illnesses that have nothing to do with the leukaemia.
Your Specialists
Meet CION's oncologists. Bring your family history or genetic report to them.
Our medical oncologists see people with a strong family history of cancer, arrange genetic counselling and testing where it fits, and plan the checks that follow.
Medical Oncologist
Dr. C. Raghavendra Reddy
MBBS(Gold Medal), DNB(General Medicine), DM(Medical Oncology)(Gold Medal)
Medical Oncologist
Dr. Bharati Devi Gorantla
MBBS, MD(General Medicine), DM(Medical Oncology)(Adyar,Chennai), ECMO, MRCP SCE(UK)
Medical Oncologist
Dr. Owais Mohammed
MBBS, MD (General Medicine), DrNB (Medical Oncology), ECMO, MRCP SCE (Medical Oncology) (UK)
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Sources
- Clinical Pharmacogenetics Implementation Consortium (CPIC) — CPIC Guideline for Thiopurines and TPMT and NUDT15
- NCBI Medical Genetics Summaries — Mercaptopurine Therapy and TPMT and NUDT15 Genotype
- MedlinePlus Genetics — Thiopurine S-methyltransferase deficiency
- National Cancer Institute — Childhood Acute Lymphoblastic Leukemia Treatment (PDQ) - Patient Version
This page is general information, not a prescription. Do not change or stop any treatment based on what you read here. If anything is worrying you, contact your own treating team — or call our helpline and we will help you reach the right specialist.
Keep reading
Related pages
Why NUDT15 matters especially in South AsiaWhy the newer gene is often the more important one in IndiaThiopurine dosing in childhood leukaemia maintenanceHow the dose is managed at home over the long maintenance phaseWhat a poor metaboliser result meansIf the report says poor metaboliser, start hereIntermediate metaboliser results and dose adjustmentThe middle result, and how the dose is found
Talk to us
Not sure whether both genes were tested?
Bring the report and the prescription, and we will check which genes were covered and what the result means for the dose. One helpline serves every CION centre.