Also Known As
Janus Kinase 2
Formal Name
JAK2 V617F; JAK2 Exon 12 Mutation
This article was last reviewed on
This article waslast modified on
22 April 2018.
At a Glance
Why Get Tested?

To help diagnose bone marrow disorders characterised by overproduction of one or more types of blood cells known as myeloproliferative neoplasms (MPNs)

When To Get Tested?

When your doctor suspects that you may have a bone marrow disorder, including polycythaemia vera, essential thrombocythaemia, or primary myelofibrosis

Sample Required?

A blood sample taken from a vein in your arm; sometimes a sample of bone marrow

Test Preparation Needed?

None

On average it takes 7 working days for the blood test results to come back from the hospital, depending on the exact tests requested. Some specialist test results may take longer, if samples have to be sent to a reference (specialist) laboratory. The X-ray & scan results may take longer. If you are registered to use the online services of your local practice, you will be able to access your results online.

If the doctor wants to see you about the result(s), you will be offered an appointment. If you are concerned about your test results, you will need to arrange an appointment with your doctor so that all relevant information including age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), can be considered.

Lab Tests Online-UK is an educational website designed to provide patients and carers with information on laboratory tests used in medical care. We are not a laboratory and are unable to comment on an individual's health and treatment.

Reference ranges are dependent on many factors, including patient age, gender, sample population, and test method, and numeric test results can have different meanings in different laboratories.

For these reasons, you will not find reference ranges for the majority of tests described on this web site. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the test(s) to obtain the reference range if you do not have the lab report.

For more information on reference ranges, please read Reference Ranges and What They Mean.

What is being tested?

The Janus Kinase 2 or JAK2 gene provides instructions for making the JAK2 protein, which promotes cell growth and division, and is especially important for controlling blood cell production from stem cells located within the bone marrow. This test looks for mutations in JAK2 that are associated with bone marrow disorders caused by an overproduction of blood cells.

The bone marrow disorders caused by JAK2 mutations are known as myeloproliferative neoplasms (MPNs), where the bone marrow overproduces white blood cells, red blood cells, and/or platelets. Some of the MPNs most commonly associated with JAK2 are: polycythaemia vera (PV), where bone marrow makes too many red blood cells; essential thrombocythaemia (ET), where there are too many platelet-producing cells (megakaryocytes) in the bone marrow; and primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis or agnogenic myeloid metaplasia, where there are too many platelet-producing cells and cells that produce scar tissue in the bone marrow.

The primary JAK2 test is JAK2 V617F, named for a mutation at a specific location in the JAK2 gene. JAK2 V617F mutation is acquired as opposed to inherited and results in the change of a single DNA nucleotide base pair. In JAK2, this kind of mutation, called a point mutation, leads to a change in the protein building block that the gene codes for, replacing the normal amino acid valine (V) with phenylalanine (F). This amino acid change results in a JAK2 protein that is constantly "on," leading to uncontrolled blood cell production.

As many as 95% of people with PV and 50-75% of people with ET or PMF are positive for the JAK2 V617F mutation. Additionally, the mutation is also infrequently detected in people with chronic myelomonocytic leukaemia (CMML), primary acute myeloid leukaemia (AML), myelodysplastic syndrome (MDS), and chronic myeloid leukaemia (CML).

Mutations in other coding portions (called exons; they code for proteins) of the JAK2 gene are also associated with MPNs. There are tests to detect changes in JAK2 exon 12. Two to five percent of people with PV have an exon 12 mutation.

The presence of a JAK2 mutation helps a healthcare professional make a definitive diagnosis of MPN (PV, ET or PMF), but the absence of a JAK2 mutation does not rule out MPN. In 2008, the World Health Organization (WHO) revised its diagnostic criteria for PV and ET, adding the presence of JAK2 mutation as a criterion..

The finding of a JAK2 mutation associated with uncontrolled blood cell growth in MPNs also suggests a possible therapeutic approach to some MPNs. As an example, one JAK2 inhibitor has been approved for the treatment of intermediate and high risk myelofibrosis.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm. Bone marrow can also be used to detect the mutation.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

Accordion Title
Common Questions
  • How is it used?

    The JAK2 mutation test may be used, along with other tests such as erythropoietin, to help diagnose bone marrow disorders that lead to overproduction of blood cells. These conditions are known as myeloproliferative neoplasms (MPNs).

    The MPNs most commonly associated with JAK2 mutation are: polycythaemia vera (PV), where bone marrow makes too many red blood cells; essential thrombocythaemia (ET), where there are too many platelet-producing cells in the bone marrow; and primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis or agnogenic myeloid metaplasia, where there are too many platelet-producing cells and cells that produce scar tissue in the bone marrow. The JAK2 mutation test is typically requested as a follow-up test if a person has a significantly increased haemoglobin and/or platelet count and the healthcare professional suspects that the person may have an MPN.

    JAK2 V617F is named for a mutation at a specific location in the JAK2 gene and is the primary genetic test for JAK2 mutations that lead to MPNs. JAK2 mutations are acquired as opposed to inherited and result in the change of a single DNA nucleotide base pair, called a point mutation. This change results in a JAK2 protein that is constantly "on," leading to uncontrolled blood cell growth.

    Mutations in other coding portions (called exons; they code for protein) of the JAK2 gene are also associated with MPNs. There is a test also available to detect changes in JAK2 exon 12. Two to five percent of people with PV have an exon 12 mutation.

    The presence of a JAK2 mutation helps a healthcare professional make a definitive diagnosis of MPN (PV, ET or PMF), but the absence of a JAK2 mutation does not rule out MPN. In 2008, the World Health Organization (WHO) revised its diagnostic criteria for PV and ET, adding the presence of JAK2 mutation as a criterion. The finding of a JAK2 mutation associated with uncontrolled blood cell growth in MPN also suggests a possible therapeutic approach to some MPN. As an example, one JAK2 inhibitor has been approved for the treatment of intermediate and high risk myelofibrosis.

  • When is it requested?

    The JAK2 V617F test may be requested along with other tests when a healthcare professional suspects that a person has a blood disorder known as a myeloproliferative neoplasm (MPN), especially polycythaemia vera (PV), essential thrombocythaemia (ET), or primary myelofibrosis (PMF). Many routine laboratory results such as a full blood count (FBC) reveal abnormal results associated with these MPNs, and someone may also have signs and symptoms that suggest an MPN.

    Sometimes people with MPNs may have no symptoms or a few, relatively mild ones that may be present for years before being recognised as an MPN, often during a routine health check. However, if certain signs and symptoms appear, a health care provider may suspect that someone has one of these MPNs. They have many signs and symptoms in common, for example:

    • Weakness and fatigue
    • Shortness of breath during exertion
    • Loss of appetite and weight loss
    • Enlarged spleen (splenomegaly)
    • Bleeding and bruising, due to low and/or abnormal platelets
    • Night sweats
    • Bone and joint pain
    • A pale appearance due to anaemia (when red blood cells are decreased)
    • Frequent infections

    Polycythaemia vera (PV) may also be suspected when symptoms such as headaches, dizziness, visual distortion, itching and paresthesia (abnormal skin sensation, such as tickling, tingling or numbness) appear. In PV, there are an excess number of red blood cells and the resulting blood thickening may lead to complications such as stomach ulcers, kidney stones, venous thrombosis, stroke, and rarely to congestive heart failure. Since PV symptoms may be slow to appear, it is often discovered during routine blood tests.

    Those with essential thrombocythaemia (ET) usually have no symptoms, but some may develop inappropriate blood clots (thrombosis) or bleeding (haemorrhage) because there are increased numbers of platelets produced that may not function properly. A blood clot could also cause a temporary interruption of blood flow to part of the brain (a transient ischemic attack) or stroke. Other symptoms from blood clots or excessive bleeding may include tingling in the hands and feet, headaches, dizziness, nosebleeds, and easy bruising.

    Primary myelofibrosis (PMF) is a serious disorder that leads to bone marrow scarring and can eventually evolve into other, more serious forms of leukaemia. However, some people with PMF have no symptoms for years. People who do have symptoms may have those that are associated with severe anaemia, such as fatigue and weakness. A JAK2 mutation test may be done if routine laboratory tests suggest PMF.

    The JAK2 exon 12 test may be requested when the JAK2 V617F test is negative and the doctor still suspects PV. 

  • What does the test result mean?

    If the JAK2 V617F mutation is detected and the person has other supporting clinical signs, then it is likely that the person has an MPN. Other testing, such as a bone marrow biopsy, may need to be performed to determine which MPN the person has and to evaluate its severity.

    If the JAK2 V617F test is negative but a JAK2 exon 12 mutation is detected and the person has supporting clinical signs, then it is likely that the person has polycythaemia vera.

    If the person is negative for all JAK2 mutations, the person may still have an MPN. The person could have a JAK2-negative MPN or their JAK2 mutation was not detected during testing. The JAK2 tests are performed on the genetic material found in granulocytes (from blood or bone marrow) and red cell precursors (from bone marrow), but not all granulocytes and red cell precursors will possess the JAK2 mutations. The proportion of affected cells will vary from person to person and may change over time. If there is only a small number in the blood sample tested, then it is possible that the mutation will not be detected.

    The presence of other mutations can help confirm the diagnosis of an MPN. Recently, mutations in the CALR (calreticulin) gene have been associated with 30-40% of JAK2-negative MPNs. Mutations in MPL account for 5% of JAK2-negative MPNs.

  • Is there anything else I should know?

    A few laboratories are offering both qualitative and quantitative JAK2 V617F tests. Some healthcare professionals may request a quantitative test to monitor the change in the number of cells with the JAK2 V617F mutation over time. However, the quantitative test is not performed commonly as a standard practice and its clinical utility has yet to be strongly established.

  • Can this test be done in my doctor's surgery?

    JAK2 mutation testing must be performed in a laboratory that performs molecular testing. It is not offered by every laboratory and must often be sent out to a reference laboratory.

  • Should everyone have a JAK2 mutation test performed?

    Testing is not indicated unless someone has signs or symptoms that suggest an MPN. This is not a test that would be appropriate to use to screen the general population.

  • Is there any reason to repeat a JAK2 mutation test?

    A doctor may repeat this test if it was negative and the doctor feels that the mutation may have been missed. One reason it might be negative is that the proportion of your cells that have the JAK2 V617F mutation may be low. Currently, the test is not nationally standardised, so the sensitivity of the test may vary somewhat from laboratory to laboratory. A second test done at a later time and/or sent to a different laboratory may detect the JAK2 V617F mutation if it is present. Also, some doctors may request a quantitative test periodically to monitor the change in the number of cells with the JAK2 V617F mutation over time. Results from repeated quantitative tests may be useful in monitoring the effectiveness of treatment if ongoing research shows that the JAK2 gene is an appropriate target for MPN therapies.

  • Are there other genetic tests associated with MPNs?

    Yes, mutations in the myeloproliferative leukaemia (MPL) gene have been associated with 5% ET and PMF but not with PV. Recently, mutations in the CALR (calreticulin) gene have been associated with 30-40% of JAK2-negative MPNs (ET and PMF) . Genetic testing is also sometimes used to check for the presence or absence of a Philadelphia (Ph') chromosome or a bcr-abl translocation (see BCR-ABL) in a person suspected of having chronic myelogenous leukaemia.