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JAK2 Mutation

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Also known as: Janus Kinase 2
Formal name: JAK2 V617F; JAK2 Exon 12 Mutation

The Test Sample

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: polycythemia vera (PV), where bone marrow makes too many red blood cells; essential thrombocythemia (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 leukemia (CMML), primary acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (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 health care provider 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. However, consensus has not yet been achieved for the optimal diagnostic criteria for PV.

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.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

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

No test preparation is needed.