JAK2 Exon 12, 13, 14 and 15 Mutation Analysis by NGS

Molecular testing of blood or bone marrow is useful in the evaluation of suspected myeloproliferative neoplasms (MPN). This test will assess mutations in JAK2 exons 12, 13, 14 and 15.

The JAK2 (Janus kinase 2) gene encodes for a non-receptor protein tyrosine kinase that activates cytokine and growth factor signaling. The V617F (c.1849 G>T) mutation results in constitutive activation of JAK2 and downstream STAT5 and ERK signaling. The V617F mutation is observed in approximately 95% of polycythemia vera (PV), 60% of essential thrombocythemia (ET) and primary myelofibrosis (PMF). It is also infrequently present (3-5%) in myelodysplastic syndrome, chronic myelomonocytic leukemia and other atypical chronic myeloid disorders. A small percentage of JAK2 mutation-positive patients (3.3%) contain other non-V617F mutations within exons 12 to 15. In particular, mutations in exon 12 of JAK2 have been described in approximately 3% of patients with PV. JAK2 mutation allele burden correlates with clinical phenotype, with low levels of mutant allele characterized by thrombocytosis, intermediate levels with erythrocytosis and high mutant allele burden, correlating with enhanced myelopoiesis of the BM, leukocytosis, increasing spleen size and circulating CD34-positive cells.