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JAK/STAT pathway dysregulation is a key driver of PV
- Approximately 99% of patients exhibit an activating JAK2 mutation in either JAK2V617F exon 14 or JAK2 exon 12[1]
- This leads to proliferation of haematopoietic cells and a chronic inflammatory state caused by overproduction of cytokines[2],[3]
JAKAVI is the only drug to provide inhibition of both JAK1 and JAK2
- JAKAVI has been shown in vitro to bind to the kinase domain of JAK1 and JAK2 and inhibit JAK1 and JAK2 signalling[4]
- JAKAVI inhibits JAK stimulation of STAT and downstream effects on cellular proliferation[4]
JAK, Janus kinase.
HU is a cytoreductive therapy and does not alter the natural history of the disease[5]
References
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Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 2010;24(6):1128-1138.
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Levine RL, Pardanani A, Tefferi A, Gilliland DG. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer. 2007;7(9):673-683.
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Harrison CN, Vannucchi AM, Kiladjian JJ, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016;30(8):1701-1707.
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Data on file. JAKAVI (ruxolitinib) Core Data Sheet. 2015. Novartis Pharma AG. Basel, Switzerland.
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Mughal T, Vaddi K, Sarlis NJ, Verstovsek S. Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes. Int J Gen Med. 2014;7:89-101.