Splenomegaly in myelofibrosis--new options for therapy and the therapeutic potential of Janus kinase 2 inhibitors. J Hematol Oncol 2012 Aug 01;5:43
Date
08/03/2012Pubmed ID
22852872Pubmed Central ID
PMC3464878DOI
10.1186/1756-8722-5-43Scopus ID
2-s2.0-84864416539 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
Splenomegaly is a common sign of primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), and post-essential thrombocythemia myelofibrosis (post-ET MF) that is associated with bothersome symptoms, which have a significant negative impact on patients' quality of life. It may also be present in patients with advanced polycythemia vera (PV) or essential thrombocythemia (ET). Until recently, none of the therapies used to treat MF were particularly effective in reducing splenomegaly. The discovery of an activating Janus kinase 2 (JAK2) activating mutation (JAK2V617F) that is present in almost all patients with PV and in about 50-60 % of patients with ET and PMF led to the initiation of several trials investigating the clinical effectiveness of various JAK2 (or JAK1/JAK2) inhibitors for the treatment of patients with ET, PV, and MF. Some of these trials have documented significant clinical benefit of JAK inhibitors, particularly in terms of regression of splenomegaly. In November 2011, the US Food and Drug Administration approved the use of the JAK1- and JAK2-selective inhibitor ruxolitinib for the treatment of patients with intermediate or high-risk myelofibrosis, including PMF, post-PV MF, and post-ET MF. This review discusses current therapeutic options for splenomegaly associated with primary or secondary MF and the treatment potential of the JAK inhibitors in this setting.
Author List
Randhawa J, Ostojic A, Vrhovac R, Atallah E, Verstovsek SAuthor
Ehab L. Atallah MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
HumansJanus Kinase 2
Primary Myelofibrosis
Protein Kinase Inhibitors
Splenomegaly