Clinical Information

The Janus kinase 2 (JAK2) gene codes for a tyrosine kinase (JAK2) 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 variant in JAK2 characterized as c.G1849T; p. Val617Phe (V617F). This variant is identified overall in approximately two-thirds of all MPN,(1-3) but the prevalence varies by MPN subtype. The JAK2 V617F variant is present in 95% to 98% of polycythemia vera patients, 50% to 60% of primary myelofibrosis (PMF) patients, and 50% to 60% of essential thrombocythemia (ET) patients. It has infrequently been described in other myeloid neoplasms, including chronic myelomonocytic leukemia and myelodysplastic syndrome.(4) This variant is not seen in chronic myelogenous leukemia or reactive conditions with elevated blood counts. Detection of the JAK2 V617F variant is useful to help establish the diagnosis of MPN. However, a negative JAK2 V617F result does not indicate absence of an MPN. Other important molecular markers in BCR-ABL1-negative MPN include CALR exon 9 variant (20%-30% of PMF and ET) and MPL exon 10 variant (5%-10% of PMF and 3%-5% of ET). Variants in JAK2, CALR, and MPL are essentially mutually exclusive.