Medical College of Wisconsin
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Emerging drugs for myelofibrosis. Expert Opin Emerg Drugs 2012 Dec;17(4):555-70

Date

11/29/2012

Pubmed ID

23186315

Pubmed Central ID

PMC5009610

DOI

10.1517/14728214.2012.748748

Scopus ID

2-s2.0-84870443079 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

INTRODUCTION: 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.

AREAS COVERED: 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.

EXPERT OPINION: 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.

Author List

Atallah E, Verstovsek S

Author

Ehab L. Atallah MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Anemia
Animals
Cytokines
Drug Design
Hematopoiesis
Humans
Janus Kinase 1
Janus Kinase 2
Nitriles
Primary Myelofibrosis
Pyrazoles
Pyrimidines
Quality of Life
Splenomegaly