From the Guidelines
JAK2 mutation testing should be ordered as a first-line investigation in patients with clinical and laboratory findings suggestive of a myeloproliferative neoplasm (MPN). This is particularly indicated when patients present with unexplained erythrocytosis, thrombocytosis, leukocytosis, splenomegaly, or unexplained thrombosis, especially in unusual sites like splanchnic veins 1. The JAK2 V617F mutation is present in approximately 95% of polycythemia vera cases and 50-60% of essential thrombocythemia and primary myelofibrosis cases.
Some key points to consider when ordering JAK2 mutation testing include:
- The presence of JAK2 mutation is a major diagnostic criterion for polycythemia vera (PV) and essential thrombocythemia (ET) 1
- If JAK2 V617F testing is negative but clinical suspicion remains high for polycythemia vera, additional testing for JAK2 exon 12 mutations should be performed
- For patients with suspected MPN who are negative for JAK2 mutations, further testing for CALR and MPL mutations is recommended, as these can be present in JAK2-negative essential thrombocythemia and primary myelofibrosis 1
- Early JAK2 testing is valuable because a positive result strongly supports an MPN diagnosis and helps distinguish MPNs from reactive conditions with similar presentations, guiding appropriate treatment decisions and management strategies
According to the most recent and highest quality study, the European LeukemiaNet (ELN) recommends JAK2 mutation testing as a first-line investigation in patients with suspected MPN 1. This recommendation is based on the critical appraisal of evidence using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology.
In terms of specific diagnostic criteria, the World Health Organization (WHO) 2016 diagnostic criteria for chronic myeloproliferative neoplasms include the presence of JAK2 mutation as a major criterion for PV and ET 1. The presence of JAK2 mutation is also a key factor in distinguishing MPNs from reactive conditions with similar presentations.
Overall, JAK2 mutation testing is a crucial diagnostic tool in the evaluation of patients with suspected MPN, and should be ordered as a first-line investigation in patients with clinical and laboratory findings suggestive of MPN.
From the Research
Ordering JAK2 Mutation Test
The JAK2 mutation test is used to diagnose and monitor myeloproliferative neoplasms (MPNs), a group of disorders that affect blood cell production.
- The test is typically ordered for patients with suspected MPN, including those with polycythemia vera, essential thrombocythemia, and primary myelofibrosis 2, 3.
- The JAK2 V617F mutation is the most common mutation associated with MPNs, and is found in almost all patients with polycythemia vera and approximately 50% of patients with essential thrombocythemia and primary myelofibrosis 2.
- Other JAK2 mutations, such as those in exon 12, may also be associated with MPNs, and molecular testing should not be restricted to the V617F and exon 12 mutations 3.
- The test may be ordered for patients with symptoms such as anemia, thrombocytosis, or splenomegaly, or for those with a family history of MPN 4, 5.
- The JAK2 mutation test can help diagnose MPN and guide treatment decisions, including the use of JAK inhibitors, which have been shown to improve symptoms and quality of life for patients with MPN 5, 6.
Clinical Considerations
- The JAK2 mutation test should be considered for patients with suspected MPN, particularly those with polycythemia vera, essential thrombocythemia, and primary myelofibrosis 2, 3.
- The test may be ordered in conjunction with other diagnostic tests, such as bone marrow biopsy and blood cell count, to confirm a diagnosis of MPN 4, 5.
- Patients with a positive JAK2 mutation test result may be eligible for treatment with JAK inhibitors, which can help manage symptoms and improve quality of life 5, 6.