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Cited by 43Myeloproliferative Neoplasms: Diagnosis and TreatmentAcute Myeloid Leukemia ResearchPlatelet Disorders and Treatments

Therapeutic potential of Janus-activated kinase-2 inhibitors for the management of myelofibrosis

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Verstovsek, Srdan·2010·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-09-2836PMC PMC5017533
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Abstract

Myelofibrosis (either primary or postpolycythemia vera/essential thrombocythemia) is a chronic and debilitating myeloproliferative neoplasm for which there is no well-accepted standard of care. Clinical manifestations of this disease (e.g., cytopenias, splenomegaly, bone marrow fibrosis) and constitutional symptoms (e.g., hypercatabolic state, fatigue, night sweats, fever) create significant treatment challenges. For example, progressive splenomegaly increases the risk for more serious clinical sequelae (e.g., portal hypertension, splenic infarction). Myelofibrosis arises from hematopoietic stem cells or early progenitor cells. However, the molecular mechanisms underlying its pathogenesis and clinical presentation are poorly understood, delaying the development of effective and targeted treatments. Recent studies have implicated mutations that directly or indirectly lead to the deregulated activation of Janus-activated kinase 2 (JAK2). Appreciation for the activation of JAK2 and the importance of increased levels of circulating proinflammatory cytokines in the pathogenesis and clinical manifestations of myelofibrosis has led to novel therapeutic agents targeting JAKs. This review will briefly discuss the origins of the JAK2 hypothesis, the clinical relevance of JAK2 mutations in myelofibrosis, and recent clinical progress in targeting JAKs as a therapeutic intervention for patients with this chronic and debilitating disease. Clin Cancer Res; 16(7); 1988–96. ©2010 AACR.

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Authors
Verstovsek, S.
Affiliations
Author's Affiliation: M.D. Anderson Cancer Center, Houston, Texas
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2010-03-31
Volume
16
Issue
7
Pages
1988-1996
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-09-2836
PMC
PMC5017533
OpenAlex
W2126103822
Cited by
43
References
0
Citations by year
2025: 1 · 2020: 4 · 2019: 1 · 2018: 1 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 4 · 2012: 5
FWCI
4.57
Type
journal article
Language
en
Open access
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (P30CA016672)
Topics
  • Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
Keywords
myelofibrosis, JAK2 inhibitors, JAK2 mutation, myeloproliferative neoplasms, post-polycythemia vera myelofibrosis, essential thrombocythemia, splenomegaly, inflammatory cytokines, targeted therapy
MeSH terms
Animals, Humans, Models, Biological, Protein Kinase Inhibitors, Mutant Proteins, Janus Kinase 2, Cytostatic Agents, Primary Myelofibrosis

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