JAK2 Mutation Testing Guidelines

Indications for JAK2 Testing

Primary care providers should order JAK2V617F testing in patients presenting with unexplained erythrocytosis, defined as hemoglobin >18.5 g/dL in males or >16.5 g/dL in females, as recommended by the European LeukemiaNet 1
JAK2V617F testing is also recommended for patients with persistent thrombocytosis, suspected myelofibrosis, or splanchnic vein thrombosis, particularly in younger patients without typical risk factors, according to the European LeukemiaNet 1, 2
The American Society of Hematology suggests that JAK2V617F testing should be considered in patients with suspected myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis 1, 2

The European LeukemiaNet recommends that JAK2V617F should be the first test ordered in patients suspected of any Philadelphia chromosome-negative MPN, with a sensitivity of 95% for polycythemia vera and 50-60% for essential thrombocythemia and primary myelofibrosis 1, 2, 4
If JAK2V617F is negative, the International Society on Thrombosis and Haemostasis suggests testing for JAK2 exon 12 mutations in patients with erythrocytosis, and CALR mutations first, then MPL mutations in patients with thrombocytosis or myelofibrosis 1, 2

The European LeukemiaNet recommends that patients with positive JAK2 results or persistent clinical suspicion despite negative molecular testing should be referred to hematology for bone marrow biopsy and further evaluation, with a strength of evidence level of 1A 1, 2
The American Society of Hematology suggests that bone marrow examination is necessary for definitive diagnosis in most cases, except polycythemia vera with hemoglobin >18.5 g/dL in males or >16.5 g/dL in females, with a strength of evidence level of 1B 1, 2

The International Society on Thrombosis and Haemostasis recommends that the JAK2V617F detection assay should be sensitive enough to detect a mutant allele burden as low as 1-3%, with a strength of evidence level of 1A 6
The European LeukemiaNet suggests that primary care providers should ensure their laboratory uses appropriately sensitive methods, such as quantitative PCR or high-resolution melting analysis, with a strength of evidence level of 1B 6