Targeting myeloproliferative neoplasms with JAK inhibitors

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Purpose of Review: The discovery of JAK2V617F and other JAK-STAT-activating mutations in BCR-ABL1-negative myeloproliferative neoplasms (MPN) has led to the development of small-molecule ATP-mimetics that inhibit wild-type and mutant JAK. Here, we review the current experience with JAK inhibitors used for the treatment of myelofibrosis and polycythemia vera/essential thrombocythemia. Recent Findings: Consistent with the clonal complexity of MPN, JAK inhibitors have not thus far shown disease-modifying activity; treatment with these agents has however shown clinically meaningful benefits, particularly decreased splenomegaly and improvement in constitutional symptoms, in myelofibrosis patients. Although these benefits accrue with both JAK-2 (TG101348) and JAK-1/2 (INCB018424, CYT387) inhibitors, the mode of action (predominant anticlonal versus anticytokine activity) may be different between the two groups. It is possible that an optimal balance between JAK-1-inhibitory and JAK-2-inhibitory activities may broaden the therapeutic activity (i.e. anemia improvement), as has been preliminarily seen (CYT387). Summary: Although JAK inhibitors have important benefits in myelofibrosis therapy, their role in polycythemia vera/essential thrombocythemia treatment is still being defined. The optimal dosing strategy and feasibility for combination with other therapeutic agents remains to be established. Another challenge is the identification of robust primary end-points that will support labeling claims for JAK inhibitors for the aforementioned indications.

Original languageEnglish (US)
Pages (from-to)105-110
Number of pages6
JournalCurrent opinion in hematology
Volume18
Issue number2
DOIs
StatePublished - Mar 1 2011

Keywords

  • JAK2
  • JAK2V617F
  • kinase inhibitor
  • myelofibrosis
  • polycythemia
  • thrombocythemia

ASJC Scopus subject areas

  • Hematology

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