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 infectionsPolycythaemia 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.
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 …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. See MoreSee Less
