JAK2 Mutation

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  • Also Known As:
  • Janus Kinase 2
  • Formal Name:
  • JAK2 V617F|JAK2 Exon 12 Mutation
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Bone Marrow Aspiration and Biopsy

At a Glance

Why Get Tested?

To help diagnose bone marrow disorders known as myeloproliferative neoplasms (MPNs) in which the bone marrow produces too many of one or more types of blood cells

When To Get Tested?

When your health care practitioner suspects that you may have a bone marrow disorder, including polycythemia vera, essential thrombocythemia, or primary myelofibrosis

Sample Required?

A blood sample drawn from a vein in your arm or sometimes a sample of bone marrow

Test Preparation Needed?

None

What is being tested?

The Janus Kinase 2 gene, called JAK2 for short, provides instructions to cells for making the JAK2 protein. This protein promotes cell growth and division and is especially important for controlling blood cell production within the bone marrow. This test looks for mutations in JAK2 that are associated with bone marrow disorders caused by the production of too many blood cells.

The bone marrow disorders caused by JAK2 mutations are known as myeloproliferative neoplasms (MPNs) in which the bone marrow produces too many white blood cells, red blood cells, and/or platelets. Some of the MPNs most commonly associated with JAK2 mutations are:

  • Polycythemia vera (PV)—the bone marrow makes too many red blood cells
  • Essential thrombocythemia (ET)—there are too many platelet-producing cells (megakaryocytes) in the bone marrow
  • Primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis or agnogenic myeloid metaplasia—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, replaces the normal amino acid valine (abbreviated V) with phenylalanine (abbreviated F). This amino acid change results in a JAK2 protein that is constantly “on,” leading to uncontrolled blood cell production.

Other mutations in the JAK2 gene are also associated with MPNs. Over 50 different mutations have been identified. There are tests available to detect mutations in JAK2 exon 12 and to identify other non-V617F mutations.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm. Sometimes a bone marrow aspiration and biopsy may be done to collect a sample for testing.

Common Questions

How is it used?

The JAK2 mutation test may be used, along with other tests such as CALR mutation and MPL mutation testing, to help diagnose bone marrow disorders that lead to the production of too many blood cells. These disorders are known as myeloproliferative neoplasms (MPNs).

The JAK2 mutation test is typically ordered as a follow-up test if a person has a significantly increased hemoglobin, hematocrit, red blood cells and/or platelet count and the healthcare practitioner suspects that the person may have an MPN, especially polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis (PMF).

The primary genetic test for JAK2 mutations that lead to MPNs is JAK2 V617F, named for a mutation at a specific location in the JAK2 gene. It is typically ordered first. If it is negative, then tests for other mutations in the JAK2 gene that are also associated with MPNs, such as JAK2 exon 12, may be used to help make a diagnosis.

When is it ordered?

The JAK2 V617F test may be ordered along with other tests when a healthcare practitioner suspects that a person has a myeloproliferative neoplasm (MPN). Testing may be done when routine laboratory test results, such as from a complete blood count (CBC), reveal abnormal results associated with these MPNs.

Sometimes people with MPNs may have no symptoms or a few, relatively mild ones that may be present for years before being recognized as an MPN, often during a routine physical. However, a healthcare practitioner may suspect an MPN and order testing when a person has, for example:

  • Enlarged spleen (splenomegaly) or liver (hepatomegaly)
  • A blood clot in a vein or artery
  • Heart attack
  • Stroke or transient ischemic attack
  • Bleeding
  • Headache
  • Dizziness
  • Vision problems
  • Numbness
  • Itchiness
  • Gout
  • Kidney stones
  • Fatigue
  • Shortness of breath
  • Weight loss
  • Fever

The JAK2 exon 12 test and/or a test for other non-V617F JAK2 mutations may be ordered when the JAK2 V617F test is negative and the healthcare practitioner still suspects polycythemia vera.

What does the test result mean?

A positive JAK2 V617F mutation test, along with other supporting clinical signs, means it is likely that the person tested 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.

More than 95% of people with polycythemia vera (PV) and 50-60% of people with essential thrombocythemia (ET) or primary myelofibrosis (PMF) have a JAK2 mutation, most for the JAK2 V617F mutation. Additionally, the mutation is also rarely found in people with chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML).

A negative JAK2 V617F test but a positive JAK2 exon 12 mutation or other non-V617F mutation test along with supporting clinical signs means it is likely that the person has polycythemia vera. About 3-4% of people with PV have an exon 12 mutation.

Negative results for all JAK2 mutations does not necessarily rule out an MPN—the person may have a JAK2-negative MPN or the JAK2 mutation was not detected during testing. The JAK2 tests are performed on the genetic material found in white blood cells called granulocytes (from blood or bone marrow) and red cell precursors (from bone marrow). 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 of cells that have the mutation in the blood sample tested, then it is possible that the mutation will not be detected.

In 2016, the World Health Organization (WHO) revised its diagnostic criteria for PV and ET. The presence of a JAK2 V617F or JAK2 exon 12 mutation is one of three major criteria listed for diagnosis of PV. However, consensus has not yet been achieved for the optimal diagnostic criteria for PV.

Is there anything else I should know?

The finding of a JAK2 mutation associated with uncontrolled blood cell growth in MPN 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.

A few laboratories offer both a JAK2 V617F test that detects the mutation (qualitative) and a test that measures how many of cells in the sample have the mutation (quantitative). Some healthcare practitioners may order 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 healthcare practitioner's office?

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

How long does it take for JAK2 mutation test results?

It depends on the laboratory that is performing the test. Generally, results may be available within a few weeks.

Is there any reason to repeat a JAK2 mutation test?

A health care practitioner may repeat this test if it was negative and the healthcare practitioner 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 standardized, 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 healthcare practitioners may order 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 mutations associated with MPNs?

Yes, calreticulin (CALR) gene mutations (exon 9) are found in 20-25% of adult patients with essential thrombocythemia (ET) and 25-30% of adult patients with primary myelofibrosis (PMF). In addition, mutations in the myeloproliferative leukemia (MPL) gene are seen in 2-5% of adult ET patients and 3-5% of adult PMF patients, but not with polycythemia vera (PV). PV, ET and PMF are all rare in children and adolescents and although mutations might not be as common as in adults with these same diseases, not much is known. Genetic testing is also sometimes used to check for the presence or absence of a Philadelphia (Ph’) chromosome or a BCR-ABL1 translocation in a person suspected of having chronic myeloid leukemia.

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On This Site

Tests: Bone Marrow Aspiration and Biopsy, Erythropoietin, Complete Blood Count, Blood Smear, Genetic Tests for Targeted Cancer Therapy, BCR-ABL1, CALR Mutation, Chromosome Analysis

Elsewhere On The Web

National Cancer Institute: Myeloproliferative Neoplasms
National Cancer Institute: Chronic Myeloproliferative Neoplasms
The Leukemia and Lymphoma Society: Myeloproliferative Neoplasms
MPN Research Foundation: Understanding MPNs
U.S. National Library of Medicine Genetics Home Reference: JAK2 gene
National Heart, Lung, and Blood Institute: What Is Polycythemia Vera?

View Sources

Sources Used in Current Review

Nagalla, S. and Besa, E. (2016 December 2 Updated). Polycythemia Vera Workup. Medscape Drugs and Diseases. Available online at http://emedicine.medscape.com/article/205114-workup#c5. Accessed on 1/22/17.

Lal, A. (2016 November 10 Updated). Essential Thrombocytosis Workup. Medscape Drugs and Diseases. Available online at http://emedicine.medscape.com/article/206697-workup#showall. Accessed on 1/22/17.

(© 1995–2017). JAK2 V617F Mutation Detection, Blood. Mayo Clinic Mayo Medical Laboratories. Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/88715. Accessed on 1/22/17.

(© 1995–2017). JAK2 Exon 12 and Other Non-V617F Mutation Detection, Blood. Mayo Clinic Mayo Medical Laboratories. Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/89189. Accessed on 1/22/17.

(2014 September Reviewed). Jak2 gene. Genetics Home Reference. Available online at https://ghr.nlm.nih.gov/gene/JAK2. Accessed on 1/22/17.

Kelley, T. and Salama, M. (2016 October Updated). Myeloproliferative Neoplasms – MPN. ARUP Consult. Available online at https://arupconsult.com/content/myeloproliferative-neoplasms. Accessed on 1/22/17.

Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391-2405. Available online at http://www.bloodjournal.org/content/127/20/2391?sso-checked=true. Accessed February 2017.

Hofmann I. Myeloproliferative neoplasms in children. J Hematopathol. 2015;8:143-157.

Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017;129:667-679.

Rumi E, Cazzola M. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood. 2017;129:680-692.

DeLario MR, Sheehan AM, Ataya R, et al. Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis—an entity different from adults. Am J Hematol. 2012;87:461-464.

An W, Wan Y, Guo Y, et al. CALR mutation screening in pediatric primary myelofibrosis. Pediatr Blood Cancer. 2014;61:2256-2262.

Sources Used in Previous Reviews

(2007 May). Essential or Primary Thrombocythemia. The Leukemia and Lymphoma Society [On-line information]. PDF available for download at http://www.leukemia-lymphoma.org/attachments/National/br_1178803674.pdf. Accessed July 2009.

(2009 February). What Is Polycythemia Vera? National Heart, Lung, and Blood Institute [On-line information]. Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/poly/poly_whatis.html. Accessed July 2009.

Beals, J. (2009 March 16) JAK2 Haplotypes Influence Susceptibility to Myeloproliferative Neoplasms. Medscape Medical News [On-line information]. Available online at http://www.medscape.com/viewarticle/589655. Accessed July 2009.

McMahon, C. et. al. (2007 May 25). JAK2 V617F Mutation in Patients With Catastrophic Intra-abdominal Thromboses. Medscape from American Journal of Clinical Pathology [On-line information]. Available online at http://www.medscape.com/viewarticle/556664. Accessed July 2009.

Tan, A. et. al. (2007 July 23). A Simple, Rapid, and Sensitive Method for the Detection of the JAK2 V617F Mutation. Medscape from American Journal of Clinical Pathology [On-line information]. Available online at http://www.medscape.com/viewarticle/558906. Accessed July 2009.

Vannucchi, A. et. al. (2009 March 23). Treatment Options for Essential Thrombocythemia and Polycythemia Vera. Medscape from Expert Review of Hematology [On-line information]. Available online at http://www.medscape.com/viewarticle/589735. Accessed July 2009.

(2007 March). JAK2 c.1849G>T (V617F) Mutation Quantification by Real-Time PCR. ARUP Technical Bulletin [On-line information]. PDF available for download through http://www.aruplab.com. Accessed July 2009.

(2007 March). JAK2 (V617F) Mutation by PCR. ARUP Technical Bulletin [On-line information]. PDF available for download through http://www.aruplab.com. Accessed July 2009.

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(13 Feb. 2012). Tefferi, Ayalew. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. American Journal of Hematology Continuing Education Series. Available online through http://onlinelibrary.wiley.com. Accessed June 2013.

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(Dec. 8, 2012). Kiladjian, Jean-Jacques. The spectrum of JAK2-Positive myeloproliferative neoplasms. American Society of Hematology Education Book. Available online at http://asheducationbook.hematologylibrary.org/content/2012/1/561.full. Accessed June 2013.

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