|Transcript ID (GRCh37/hg19)||ENST00000381652|
|Tumor Type||Primary Site|
This gene is a known cancer gene.
Mutations at codon R683 of JAK2, have been previously described in B-ALL (especially Down Syndrome associated B-ALL) and represent a mutational "hotspot"; Some variants at this codon (R683) are known to be activating mutations. Cases of B-ALL with JAK2 mutations tend to also show rearrangement/overexpression of CRLF2; these are potentially targetable pathway alterations. Such cases tend to have a BCR/ABL-like transcriptional signature.
JAK2 is a non-receptor tyrosine kinase that mediates signaling via the JAK-STAT pathway. The somatic, activating mutation V617F in the pseudokinase domain of JAK2 has been reported in over 90% of patients with polycythemia vera, 40-70% of essential thrombocythemia, 40-60% of primary myelofibrosis and 50% of MDS/MPN with Ring Sideroblasts and Thrombocytosis. JAK2 mutations have also been reported in CHIP. The small percentage of cases of polycythemia vera that do not carry the JAK2 V617F mutation have somatic, activating mutations in JAK2 exon 12 which typically affect the region encompassing codons 536-547 and are in-frame deletions/insertions, duplications of 8-12 amino acids or missense mutations. Mutations in JAK2 are typically mutually exclusive with mutations in the thrombopoietin receptor (MPL) and calreticulin (CALR), but JAK2 mutations may co-exist with mutations in other genes (ie, IDH1, SF3B1, TET2, ASXL1, etc). Ruxolitinib is a JAK2 inhibitor that has been approved for use in patients with intermediate- and high-risk primary myelofibrosis and is under study in other JAK2+ MPNs. Other JAK2 inhibitors (eg, Pacritinib) are also in various stages of study.