What is the Jak2 V617F mutation?

By William Aird

Jak2 V617F mutation is a G to T somatic mutation at nucleotide 1,849 in exon 14 of JAK2, leading to constitutive activation of signaling pathways downstream of the erythropoietin receptor. It occurs in 95% of patients with polycythemia vera as well as a smaller percentage of patients with other myeloproliferative neoplasms, encodes a constitutively active Janus kinase that upregulates JAK/STAT signal transduction, resulting in unregulated myeloproliferation (erythrocytosis, often with leukocytosis and/or thrombocytosis).

May occur in:

  • Polycythemia vera (95% of cases)
  • Essential thrombocythemia (50-60% of cases)
  • Primary myelofibrosis (50-60% of cases)
  • Refractory anemia with ringed sideroblasts associated with significant thrombocytosis (50% of cases)
EPOR, erythropoietin receptor; FERM = N-terminal Band 4.1, ezrin, radixin, moesin domain; JH1 and JH2 = Jak homology 1 and 2 domains; SH2 = Src homology 2 domain.

Learn more here.