Abstract:
:The myeloproliferative neoplasms (MPNs) essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are malignancies that frequently harbor the recurrent somatic point mutation JAK2(V617F). The discovery of this mutation has fueled the development of Janus kinase 2 (JAK2) inhibitors. Available results have indicated that JAK2 inhibitors are particularly effective at reducing spleen size. However, the activity of these agents is multifaceted and also involves a marked improvement of systemic symptoms and, for those agents with dual JAK1 and JAK2 inhibitory activity, a marked reduction in the levels of circulating cytokines involved in the pathogenesis of the disease. Because JAK2 inhibitors are not specific for JAK2(V617F), responses have also been observed in JAK2(V617F) -negative MPNs because of the inhibition of wild-type JAK2, which is also likely responsible for the induction of cytopenias in patients with MF and for the normalization of peripheral blood counts observed in patients with ET or PV. Given the distinct mortality and morbidity associated with ET, PV, and MF, the use of JAK2 inhibitors appears reasonable for patients with MF as well as for those with ET or PV who have become resistant or intolerant to hydroxyurea. Ongoing randomized, placebo-controlled, phase 3 trials will further delineate the role of these agents in the management of patients with MPNs. The pros and cons of JAK2 kinase inhibitor therapy are herein discussed.
journal_name
Cancerjournal_title
Cancerauthors
Quintás-Cardama A,Verstovsek Sdoi
10.1002/cncr.26359subject
Has Abstractpub_date
2012-02-15 00:00:00pages
870-7issue
4eissn
0008-543Xissn
1097-0142journal_volume
118pub_type
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