TY - JOUR
T1 - Experimental therapeutics for patients with myeloproliferative neoplasias
AU - Agrawal, Meetu
AU - Garg, Ravin J.
AU - Cortes, Jorge
AU - Kantarjian, Hagop
AU - Verstovsek, Srdan
AU - Quintas-Cardama, Alfonso
PY - 2011/2/15
Y1 - 2011/2/15
N2 - 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.
AB - 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.
KW - INCB018424
KW - JAK2 inhibitors
KW - Janus kinase (JAK2) V617F
KW - lenalidomide
KW - myeloproliferative neoplasias
KW - pegylated interferon
UR - http://www.scopus.com/inward/record.url?scp=79551718200&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79551718200&partnerID=8YFLogxK
U2 - 10.1002/cncr.25672
DO - 10.1002/cncr.25672
M3 - Review article
C2 - 20922795
AN - SCOPUS:79551718200
SN - 0008-543X
VL - 117
SP - 662
EP - 676
JO - Cancer
JF - Cancer
IS - 4
ER -