JAK 2 Mutation

Today, I am going to write about JAK 2 Mutation. This question did come out in one of MRCP Part 1 January 2010 Paper.

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.