The principal JAK2 test is called JAK2 V617F. It detects a mutation at a specific place on the JAK2 gene termed a point mutation. This causes a change in the protein produced by the gene at amino acid 617 replacing the normal valine (V) with phenylalanine (F). This change activates the JAK2 gene and promotes uncontrolled cellular growth. As many as 90% of people with PV and 50% of people with ET or PMF may be positive for the JAK2 V617F mutation.
Other JAK2 mutations are also associated with some cases of MPDs. These tests detect changes in certain portions (exons) of the gene. These mutations affect JAK2 exon 12 and JAK2 exon 13.
In 2008, the World Health Organization (WHO) updated its diagnostic criteria for PV and ET, adding as a major criterion the "presence of the JAK2 V617F or other functionally similar mutations, such as JAK2 exon 12 mutations." This update has not been accepted by everyone in the medical community, but JAK2 testing has begun to be used to help diagnose MPDs.
How is the sample collected for testing?A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?No test preparation is needed.
How is it used?The JAK2 V617F test may be used, along with other tests such as erythropoietin, to help diagnose the myeloproliferative disorders (MPDs) polycythemia vera (PV), essential thrombocythemia (ET), and agnogenic myeloid metaplasia (primary myelofibrosis, PMF). It may be ordered as a follow-up test if a person has an increased hemoglobin and/or platelet count and the doctor suspects that the person may have an MPD.
The JAK2 exon 12 and JAK2 exon 13 tests may be ordered to help diagnose PV cases that are negative for the JAK2 V617F mutation.
When is it ordered?The JAK2 V617F test may be ordered along with other tests when a doctor suspects that a person has PV, ET, or PMF because routine laboratory results such as a CBC reveal abnormal results associated with these MPDs and/or because the person has signs and symptoms that suggest an MPD.
Sometimes MPDs may have no symptoms or a few, relatively mild symptoms and may be present for years before being diagnosed, often during a routine physical. However, if certain signs and symptoms appear, a doctor may suspect that the patient has one of these MPDs. They have many signs and symptoms in common, for example:
- Weakness and fatigue
- 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 anemia (when red blood cells are decreased)
- Frequent infections
PV may also be suspected when symptoms such as headaches, dizziness, visual distortion, itching and paresthesia appear. In PV, there is an excess number of red blood cells and this may lead to complications, such as stomach ulcers, kidney stones, venous thrombosis, stroke, and rarely to congestive heart failure.
Those with ET usually have no symptoms, but some may develop inappropriate blood clots (thrombosis) or bleeding (hemorrhage) because there are increased numbers of platelets produced that do not function properly. This may cause symptoms in addition to those listed above such as tingling in the hands and feet, headaches, dizziness, nosebleeds, and easy bruising.
About one third of patients with PMF have no symptoms. People who do have symptoms may have those that are associated with anemia such as fatigue and weakness. A JAK2 test may be done if routine laboratory tests suggest PMF.
The JAK2 exon 12 and JAK2 exon 13 tests may be ordered when the JAK2 V617F test is negative and the doctor 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 he has a MPD. Other testing, such as a bone marrow biopsy, may need to be performed to determine which MPD the person has and to evaluate its severity.
If the JAK2 V617F test is negative but a JAK2 exon 12 or exon 13 mutation is detected and the person has supporting clinical signs, then it is likely that the person has PV.
If the person is negative for all JAK2 mutations, they may still have an MPD. They could have a JAK2-negative MPD or their JAK2 mutation was not detected during testing. The JAK2 tests are performed on the genetic material found in granulocyte white blood cells, but not all granulocytes will contain the JAK2 mutations. The proportion of affected cells will vary from person to person and may change over time. If there is only small number in the blood sample tested, then it is possible that the mutation will not be detected.
Is there anything else I should know?A few laboratories are offering both qualitative and quantitative JAK2 V617F tests. Some doctors may order a quantitative test to monitor the change in the number of cells with the JAK2 V617F mutation over time. Currently, the quantitative test is not performed frequently and its clinical utility has yet to be strongly established. If future research shows that the JAK2 gene is an appropriate target for MPD therapies, then it is possible that the quantitative test may be ordered periodically to monitor the effectiveness of treatment. There is still much to be learned about MPDs and about how, and if, the JAK2 mutations contribute to the progression and prognosis of MPDs.
Can this test be done in my doctor's office?
Should everyone have a JAK2 V617F test performed?
Is there any reason to repeat a JAK2 V617F test?A doctor may repeat this test if it was negative and she 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 doctors 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 MPD therapies.
Are there other genetic tests associated with MPDs?Yes, mutations in the myeloproliferative leukemia gene (MPL) have been associated with ET and PMF, but not with PV. Genetic testing is also sometimes used to check for the presence or absence of a Philadelphia (Ph') chromosome or a bcr-abl translocation in a person suspected of having the MPD CML (chronic myelogenous leukemia).