Clinical Information

The JAK2 (Janus kinase 2) 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 mutation in JAK2 characterized as c.G1849T; p. Val617Phe (V617F). The JAK2 V617F is present in 95% to 98% of polycythemia vera, and 50% to 60% of primary myelofibrosis (PMF) and essential thrombocythemia (ET). It has also been described infrequently in other myeloid neoplasms, including chronic myelomonocytic leukemia and myelodysplastic syndrome. Detection of the JAK2 V617F is useful to help establish the diagnosis of MPN. However, a negative JAK2 V617F result does not indicate the absence of 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). Mutations in JAK2, CALR, and MPL are essentially mutually exclusive. A CALR mutation is associated with decreased risk of thrombosis in both ET and PMF and confers a favorable clinical outcome in PMF patients. A triple negative (JAK2 V617F, CALR, and MPL-negative) genotype is considered a high-risk molecular signature in PMF.