title: A potential role of ruxolitinib in leukemia.
abstract: BACKGROUND
  An increased understanding of cellular signaling pathways, like the JAK?STAT pathway, and the identification of the JAK2 V617F mutation in the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), has generated great interest in the development of targeted JAK2 inhibitors. In a recently completed Phase I?II study, ruxolitinib, a selective orally available JAK1 and JAK2 inhibitor, has shown efficacy in patients with advanced myelofibrosis. Constitutive activation of the JAK?STAT pathway has also been implicated in other hematological malignancies suggesting a potential role of JAK kinase inhibitors in these malignancies.
  
  
  METHODS
  This article reviews the chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability of ruxolitinib. The literature for this article was retrieved from PubMed database searches using the keywords ?ruxolitinib?, ?INCB 018424?, ?JAK2 inhibitors? and ?leukemia?.
  
  
  CONCLUSIONS
  The JAK?STAT signaling pathway plays a vital role in leukemogenesis. Ruxolitinib, a potent JAK1 and JAK2 inhibitor, known to decrease spleen size and alleviate constitutional symptoms in myelofibrosis, represents a potentially promising agent for the treatment of leukemias by inhibiting the JAK?STAT signaling. Further studies of ruxolitinib, in patients with acute and chronic leukemias, are now needed to establish the clinical usefulness of this promising drug.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Department of Leukemia, Houston, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Naqvi
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D009570:Nitriles; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011720:Pyrazoles / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011743:Pyrimidines; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases