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Health condition

CALR and MPL mutations

CALR and MPL are the two main driver mutations found in JAK2-negative essential thrombocythaemia and myelofibrosis; identifying them confirms the diagnosis and refines the outlook.

Why trust this guide

  • 01

    Editorial team

    Written by our editorial team from the UK sources listed on each page.

  • 02

    Sourced from guidance

    Checked against current NHS and UK specialist society guidance at the time of review.

  • 03

    Current for 2026

    Reviewed on 2026-09-27 with the next review scheduled for 2027-09-27.

Key facts

The essentials at a glance.

The symptoms to recognise, when to seek help, which specialist to see, and what treatment usually involves.

  • Tested when blood counts suggest a myeloproliferative neoplasm but JAK2 is negative

  • CALR mutations are generally associated with a lower clot risk than JAK2 in ET

  • MPL mutations are the rarest of the three main drivers

  • Results shape risk scoring and treatment decisions made by a consultant haematologist

Understanding the condition

What it is and what happens next.

What causes it, how it is diagnosed, and the treatment routes available in the UK.

What it is and how it feels

About half of people with essential thrombocythaemia or myelofibrosis do not carry the JAK2 mutation. Most of these have an acquired mutation in CALR (calreticulin) or, less often, MPL, both of which activate the same growth pathway. Finding one of these mutations confirms that a raised platelet count reflects a true marrow condition rather than a reaction to something else, such as iron deficiency or inflammation.

Diagnosis and treatment routes

The mutation type feeds into modern prognostic scores. In essential thrombocythaemia, CALR-mutated disease tends to carry a lower thrombosis risk, which can tip the balance towards observation rather than count-lowering tablets. A minority of patients test negative for all three drivers ("triple negative"), and usually need a bone marrow biopsy and extended gene panels to clarify the diagnosis. In many parts of the UK, routine NHS referrals for this kind of problem can take months, whereas an initial appointment with a private consultant is typically available within around two weeks.

Seeing a specialist

Who to see, and how quickly you can be seen.

The specialist for this condition is usually a consultant haematologist. Your GP can refer you on the NHS, or you can arrange a private consultation directly.

A quiet reminder

This guide is for information, not medical advice.

Your GP knows your history and can tell you which parts apply to you. If in doubt, see them - and seek urgent care for any of the emergency symptoms described above.

Frequently asked

Common questions about CALR and MPL mutations.

Quick, plain-English answers to what people ask us most.

  • What is CALR and MPL mutations?

    CALR and MPL mutations is a recognised medical condition that can affect people in different ways, ranging from mild and easily managed to more significant, depending on the underlying cause, how early it is picked up, and how it is treated. Getting a clear diagnosis is usually the first step towards the right management plan.

  • What causes CALR and MPL mutations?

    CALR and MPL mutations can arise from a combination of factors, which may include genetics, lifestyle, environmental exposures, other underlying health conditions, or simply the normal effects of ageing on the body. In many cases no single cause is found, and several factors act together. A clinician can help identify which factors are most relevant in an individual case.

  • What are the symptoms of CALR and MPL mutations?

    Symptoms of CALR and MPL mutations vary from person to person and depend on how severe the condition is and which structures are affected. Some people notice symptoms gradually over weeks or months, while others experience a more sudden onset. Because symptoms can overlap with other conditions, a proper assessment is important to reach an accurate diagnosis rather than relying on symptoms alone.

  • Is CALR and MPL mutations serious or dangerous?

    Most cases of CALR and MPL mutations are manageable, especially when identified and treated early, but severity varies from mild and self-limiting to more significant, depending on individual circumstances. Left unassessed, some cases can lead to complications or a longer-term impact on daily life. If you are worried about your symptoms, it is always worth getting them checked rather than waiting.

  • Is CALR and MPL mutations hereditary or genetic?

    Some cases of CALR and MPL mutations have a genetic component and can run in families, while others occur without any family history at all. Having a relative with the condition may modestly increase your own risk, but it does not mean you will definitely develop it yourself. If you are concerned about a family history, mention this to your doctor, as it may occasionally influence screening or monitoring.

  • Can CALR and MPL mutations be cured, reversed or prevented?

    Outlook varies with CALR and MPL mutations: some cases resolve completely with treatment, others improve significantly but need ongoing management, and a smaller number become a long-term condition to be controlled rather than cured. Prevention strategies, such as addressing modifiable risk factors, can reduce your chances of developing it or of it recurring, but cannot guarantee against it in every case.

  • How is CALR and MPL mutations treated?

    Treatment for CALR and MPL mutations is tailored to the individual and depends on severity, underlying cause and personal circumstances. Options can range from simple lifestyle measures, monitoring and conservative treatment through to medication, specialist procedures or surgery in more significant cases. A specialist assessment helps identify which combination of treatments is most appropriate for you.

  • How long does CALR and MPL mutations last?

    The duration of CALR and MPL mutations varies considerably: some people recover within days or weeks, while others live with a more persistent or recurring condition that needs ongoing management. Response to treatment, how early it is started, and individual factors all influence the timescale. Your clinician can give you a more personalised estimate once your specific circumstances are known.

  • When is surgery needed for CALR and MPL mutations?

    Surgery is not usually the first option for CALR and MPL mutations and is generally reserved for cases where conservative treatment has not worked, symptoms are severe, or there is a significant structural problem that needs to be corrected directly. The decision depends on your specific findings, symptoms and how they are affecting your life. A specialist consultation is the best way to establish whether surgery is being considered too early, or should be considered sooner rather than later.

  • When should I see a doctor about CALR and MPL mutations, and how quickly can I be seen privately?

    It is worth seeing a doctor about CALR and MPL mutations if symptoms are persistent, getting worse, or affecting your daily life, rather than waiting to see if they settle on their own. NHS routine referrals to a specialist can currently take anywhere from around 20 to 45 weeks or more depending on your area, whereas a private consultant can typically see you within about 2 weeks. Getting an earlier assessment can help clarify the diagnosis and start the right treatment sooner.