JAK2 Mutation Screening for Diagnosis of Polycythemia Vera and Other Chronic Myeloproliferative Disorders

In early 2005, several groups of investigators reported a somatic acquired point mutation in the JAK2 (Janus kinase 2) protein in the blood and bone marrow of patients with BCR/ABL-negative chronic myeloproliferative disorders. JAK2 is a tyrosine kinase which plays an important role in normal hematopoietic growth factor signaling, and the mutation results in activation of the kinase and deregulated intracellular signaling with cell proliferation that is independent of normal growth factor control.

Using sensitive assays, the JAK2 mutation can be detected in approximately 90-95% of cases of polycythemia vera, 50-70% of patients with essential thrombocythemia, and 40-50% of cases of idiopathic myelofibrosis. The mutation has also been described in rare cases of myelodysplastic syndromes, acute myeloid leukemia, systemic mastocytosis and hypereosinophilic syndrome. It is specific for diagnosis of a clonal myeloid lineage proliferative disorder. The mutation has not been described in BCR/ABL-positive chronic myeloid leukemia, any acute or chronic lymphoid disorders, any healthy persons, or any patient with secondary polycythemia or a reactive blood count elevation. The JAK2 test promises to be very useful in distinguishing between clonal myeloproliferative disorders and reactive cellular proliferations.

Indications for the assay include the following:

Evaluation of polycythemia - the test should be ordered in addition to serum erythropoietin level.
Evaluation of an elevated platelet count, clinically not consistent with reactive thrombocytosis.
Unusual thrombotic events including abdominal or cerebral thrombosis or arterial events at a young age, which may be a presenting sign of an underlying chronic myeloproliferative disorder.

The JAK2 assay may be included in the recommended algorithm for laboratory investigation of polycythemia, as shown below. The polycythemia vera-related clinical and laboratory features referred to in the algorithm include persistent leukocytosis or thrombocytosis, microcytosis, splenomegaly, pruritis after bathing, thrombosis or erythromelalgia.

It is important to keep in mind that a positive JAK2 mutation is not specific for a particular sub-type of myeloproliferative disorder, and must be correlated with other clinical and laboratory findings for definitive diagnosis. Furthermore, a negative result does not exclude the presence of a chronic myeloproliferative disorder or other neoplastic disorder.

Sample requirement is one lavender-top tube containing at least 3mL of peripheral blood or bone marrow.