title: Therapeutic approaches in myelofibrosis.
abstract: BACKGROUND
  Myeloproliferative neoplasm (MPN)-associated myelofibrosis is the most disabling of the classical Philadelphia-negative MPNs. The discovery that a gain-of-function mutation of JAK2 (JAK2V617F) is present in more than 60% of patients with MPN-associated myelofibrosis has provided a new target for innovative treatment strategies.
  
  
  METHODS
  This review discusses the indications and limitations of conventional therapies employed for the treatment of MPN-associated myelofibrosis before reviewing the information available for new therapies, including the immunomodulatory and demethylating agents, histone deacethylase, mammalian target of rapamycin (mTOR) and JAK2- inhibitors. The Medline and ASH databases were searched for clinical trials on the medical therapy of MPN-associated myelofibrosis from early 2000 to December 2010.
  
  
  CONCLUSIONS
  Three categories of drugs have proved to have significant activity in MPN-associated myelofibrosis. Up to a 40% response rate on anemia has been reported with the immunomodulator, pomalidomide. The m-TOR inhibitor RAD-001 and various JAK2 inhibitors have documented a profound effect on splenomegaly and constitutional symptoms, with some also having activity on anemia. These new drugs will give physicians more options to tailor therapeutic choice in this challenging disease.
authors: IRCCS Policlinico S. Matteo Foundation, Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis, Viale Golgi 19, 27100 Pavia, Italy. barosig@smatteo.pv.it
authors: Giovanni
authors: G
authors: Barosi
authors: Vittorio
authors: V
authors: Rosti
authors: Alessandro M
authors: AM
authors: Vannucchi
mesh_terms: D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000503:physiopathology; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013163:Splenomegaly / Q000188:drug therapy / Q000209:etiology
chemical_list: D053614:Janus Kinase 2