title: Emerging drugs for myelofibrosis.
abstract: BACKGROUND
  Myelofibrosis (MF), a Philadelphia chromosome-negative myeloproliferative neoplasm, is a life-threatening heterogeneous disorder characterized by dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling network. The clinical hallmarks of MF are progressive splenomegaly, anemia and debilitating symptoms attributable to ineffective hematopoiesis and excessive production of proinflammatory cytokines.
  
  
  METHODS
  This review describes the pathogenesis, clinical features and current treatment of MF, clinical data for ruxolitinib, a potent oral JAK1/JAK2 inhibitor and the only therapy approved for the treatment of MF, and agents in development for the treatment of MF. Information was derived from relevant MF articles identified in the published literature and abstracts of recent congresses.
  
  
  CONCLUSIONS
  Ruxolitinib reduces spleen size and alleviates MF-related symptoms, thereby improving quality of life. Ruxolitinib may increase the risk of anemia and thrombocytopenia and does not appear to reverse bone marrow fibrosis. Studies are exploring ruxolitinib dosing strategies for patients with low platelet counts and combination therapies. Several other JAK inhibitors and other agents (i.e., immunomodulators, antifibrotic agents, anti-anemia agents, mammalian target of rapamycin [mTOR] inhibitors, epigenetic modifiers, pegylated interferon-α2a) to treat various aspects of MF (i.e., to improve blood counts or forestall marrow fibrosis) are in early clinical development.
authors.affiliation: Medical College of Wisconsin Cancer Center, Neoplastic Diseases and Related Disorders, Department of Internal Medicine, Milwaukee, WI, USA.
authors.forename: Ehab
authors.initials: E
authors.lastname: Atallah
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015195:Drug Design; D006410:Hematopoiesis; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000503:physiopathology; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D011788:Quality of Life; D013163:Splenomegaly / Q000188:drug therapy / Q000209:etiology
chemical_list: D016207:Cytokines; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2