Experimental therapeutics for patients with myeloproliferative neoplasias

Meetu Agrawal, Ravin J. Garg, Jorge Cortes, Hagop Kantarjian, Srdan Verstovsek, Alfonso Quintas-Cardama

Research output: Contribution to journalReview article

15 Scopus citations

Abstract

Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) are characterized by stem cell-derived, unrestrained clonal myeloproliferation. The World Health Organization classification system, proposed in 2008, identifies 7 distinct categories of Ph-negative MPNs including essential thrombocythemia (ET); polycythemia vera (PV); primary myelofibrosis (PMF); mastocytosis; chronic eosinophilic leukemia; chronic neutrophilic leukemia; and MPN, unclassifiable. For many years, the treatment of ET, PV, and PMF, the most frequently diagnosed Ph-negative MPNs, has been largely supportive. In recent years, that paradigm has been challenged because of the discovery of a recurrent point mutation in the Janus kinase 2 (JAK2) gene (JAK2V617F). This mutation can be detected in the vast majority of patients with PV and approximately half of patients with ET or PMF and serves as both a diagnostic marker as well as representing a putative molecular target for drug development. Several putative targeted agents with significant in vitro JAK2 inhibitory activity and various degrees of JAK2 specificity are currently undergoing clinical evaluation. Furthermore, other investigational non-tyrosine kinase inhibitor approaches such as immunomodulatory agents and pegylated interferon-α have also shown promising results in MPNs.

Original languageEnglish (US)
Pages (from-to)662-676
Number of pages15
JournalCancer
Volume117
Issue number4
DOIs
StatePublished - Feb 15 2011
Externally publishedYes

Keywords

  • INCB018424
  • JAK2 inhibitors
  • Janus kinase (JAK2) V617F
  • lenalidomide
  • myeloproliferative neoplasias
  • pegylated interferon

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Agrawal, M., Garg, R. J., Cortes, J., Kantarjian, H., Verstovsek, S., & Quintas-Cardama, A. (2011). Experimental therapeutics for patients with myeloproliferative neoplasias. Cancer, 117(4), 662-676. https://doi.org/10.1002/cncr.25672