Edit ID | Edit Comment | Time | |
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402476 | updating jak2 interp | 11/12/2018 3:41 PM |
JAK2 is a non-receptor tyrosine kinase that mediates signaling via the JAK-STAT pathway and 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 thrombocytemia and 40-60% of primary myelofibrosis. 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, among others). Ruxolitinib is a JAK2 inhibitor that has been approved for use in patients with primary myelofibrosis. In addition, several other JAK2 inhibitors are in various stages of study.
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, 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 primary myelofibrosis. In addition, several other JAK2 inhibitors are in various stages of study.