Diagnose Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Idiopathic Myelofibrosis (MF). The Janus kinase 2 gene (JAK2) codes for a tyrosine kinase (JAK2) that is associated with the cytoplasmic portion of a variety of transmembrane cytokine and growth factor receptors important for signal transduction in hematopoietic cells. Signaling via JAK2 activation causes phosphorylation of downstream signal transducers and activators of transcription (STAT) proteins (eg, STAT5) ultimately leading to cell growth and differentiation. BCR-ABL1-negative myeloproliferative neoplasms (MPN) frequently harbor an acquired single nucleotide mutation in JAK2 characterized as c.G1849T; p. Val617Phe (V617F). This mutation is identified overall in approximately two-thirds of all MPN,(1-3) but the prevalence varies by MPN subtype. The JAK2 V617F is present in 95% to 98% of polycythemia vera, 50% to 60% of primary myelofibrosis, and 50% to 60% of essential thrombocythemia. It has also been described infrequently in other myeloid neoplasms, including chronic myelomonocytic leukemia and myelodysplastic syndrome.(4) This mutation is not seen in chronic myelogenous leukemia (CML) or in reactive conditions with elevated blood counts. Detection of the JAK2 V617F is useful to help establish the diagnosis of MPN. However, a negative JAK2 V617F result does not indicate absence of a MPN. Other important molecular markers in BCR-ABL1-negative MPN include CALR exon 9 mutation (20%-30% of PMF and ET) and MPL exon 10 mutation (5%-10% of PMF and 3%-5% of ET).(5-9) Mutations in JAK2, CALR, and MPL are essentially mutually exclusive.
Also known as: JAK 2 V617F Common Mutation.