Gene affected:
JAK2 Janus kinase 2

Clinical significance
JAK2 mutations are seen in several MPNs where the risk of venous thromboembolism and AML transformation are higher that those with CALR mutations (Type 1). Certain prognostic scores take this mutation into account. JAK2 inhibitors are in current practice for PMF, although appear to work well in patients without the JAK2 mutation.

Function of gene

JAK2 is a tyrosine kinase that promotes cell proliferation and is part of the the JAK/STAT signaling pathway, with a major role in hematopoietic stem cell differentiation. JAK2 is the predominant JAK kinase activated in response to several growth factors and cytokines such as IL-3, GM-CSF and erythropoietin.

NGS panel gene coverage

Exons covered by panel 12 and 14


Myeloproliferative disorders
note that JAK2 mutation in these disorders appears to confer a greater thrombotic risk and more aggressive course than does CALR
PRV: JAK2 V617F 95%; Exon 12 mutation 3%
ET: JAK2 exon 12 50-60%; Exon 12 mutation not seen
PMF': !JAK2 exon 12 50-60%; Exon12 mutation: not seen

Myelodysplasia (8%)
MDS/MPN RARS-t (60%)
Unclear, although survival may be improved
CMML (~10%)
Associated with a proliferative form of CMML, some studies have suggested better outcomes if JAK2 mutations are present
CHIP (5-10%)
Clonal haematopoietic disease of indeterminate potential (age related clonal disease)

Note 0.5% of the normal population can be found to have the JAK2 V617F mutation; phenotypically normal individuals may present with unusual thrombosis (splanchnic or non-splanchnic) 3-5%


GeneWiki link:
Gene Wiki entry for JAK2
1. JAK2 in the general population
2. JAK and MPL in thrombosis
3. JAK mutation and outcome in myelofibrosis
4. General reference