title: JAK2 kinase inhibitors and myeloproliferative disorders.
abstract: OBJECTIVE
  The pathophysiology of Philadelphia-chromosome negative myeloproliferative disorders has significantly advanced with the discovery of JAK2V617F. The prevalence of JAK2V617F mutation has made it a much anticipated target for inhibition; this review will update and assess progress.
  
  
  RESULTS
  Many agents have been studied in preclinical trials, of which few have entered clinical trials. Data from the clinical trials are limited and mostly in the form of abstracts and reviews.
  
  
  CONCLUSIONS
  The prevalence of the JAK2V617F mutation in the classic Philadelphia-chromosome negative myeloproliferative disorders has made it a much anticipated target for inhibition. Present in greater than 90% of patients with polycythemia vera and approximately 50% of patients with essential thrombocythemia and primary myelofibrosis, it has been hoped that targeted inhibition of JAK2V617F would achieve similar disease control as imatinib mesylate has produced in chronic myeloid leukemia. However, JAK2V617F in the Philadelphia-chromosome negative myeloproliferative disorders, unlike bcr/abl tyrosine kinase in chronic myeloid leukemia, is not a causative but rather a secondary somatic mutation. As the JAK2 inhibitors move into phase III clinical trials, their efficacy and role in therapy is becoming clearer; however, there are still many questions needing answers.
authors.affiliation: Hematology and Medical Oncology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chen
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000037:antagonists & inhibitors / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D053614:Janus Kinase 2