JAK2 kinase inhibitors and myeloproliferative disorders

Andrew Chen, Josef T. Prchal

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Purpose of review: The pathophysiology of Philadelphia-chromosome negative myeloproliferative disorders has significantly advanced with the discovery of JAK2V617F. The prevalence of JAK2V617F mutation has made it a much anticipated target for inhibition; this review will update and assess progress. Recent findings: Many agents have been studied in preclinical trials, of which few have entered clinical trials. Data from the clinical trials are limited and mostly in the form of abstracts and reviews. Summary: The prevalence of the JAK2V617F mutation in the classic Philadelphia-chromosome negative myeloproliferative disorders has made it a much anticipated target for inhibition. Present in greater than 90% of patients with polycythemia vera and approximately 50% of patients with essential thrombocythemia and primary myelofibrosis, it has been hoped that targeted inhibition of JAK2V617F would achieve similar disease control as imatinib mesylate has produced in chronic myeloid leukemia. However, JAK2V617F in the Philadelphia-chromosome negative myeloproliferative disorders, unlike bcr/abl tyrosine kinase in chronic myeloid leukemia, is not a causative but rather a secondary somatic mutation. As the JAK2 inhibitors move into phase III clinical trials, their efficacy and role in therapy is becoming clearer; however, there are still many questions needing answers.

Original languageEnglish (US)
Pages (from-to)110-116
Number of pages7
JournalCurrent Opinion in Hematology
Volume17
Issue number2
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Philadelphia Chromosome
Myeloproliferative Disorders
Phosphotransferases
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Mutation
bcr-abl Fusion Proteins
Clinical Trials
Essential Thrombocythemia
Polycythemia Vera
Phase III Clinical Trials
Primary Myelofibrosis
Therapeutics

Keywords

  • JAK2
  • JAK2-inhibitors
  • JAK2V617F
  • Myeloproliferative disorders
  • Myeloproliferative neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

JAK2 kinase inhibitors and myeloproliferative disorders. / Chen, Andrew; Prchal, Josef T.

In: Current Opinion in Hematology, Vol. 17, No. 2, 03.2010, p. 110-116.

Research output: Contribution to journalReview article

Chen, Andrew ; Prchal, Josef T. / JAK2 kinase inhibitors and myeloproliferative disorders. In: Current Opinion in Hematology. 2010 ; Vol. 17, No. 2. pp. 110-116.
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