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Experimental therapeutics for patients with myeloproliferative neoplasias
Author(s) -
Agrawal Meetu,
Garg Ravin J.,
Cortes Jorge,
Kantarjian Hagop,
Verstovsek Srdan,
QuintasCardama Alfonso
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25672
Subject(s) - essential thrombocythemia , medicine , polycythemia vera , myelofibrosis , janus kinase 2 , myeloproliferative neoplasm , myeloproliferative disorders , philadelphia chromosome , cancer research , cancer , oncology , ruxolitinib , stem cell , gene , bone marrow , genetics , biology , chromosomal translocation , receptor
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 ( JAK2 V617F ). 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. Cancer 2011. © 2010 American Cancer Society.