TY - JOUR
T1 - Splenomegaly in myelofibrosis-new options for therapy and the therapeutic potential of Janus kinase 2 inhibitors
AU - Randhawa, Jasleen
AU - Ostojic, Alen
AU - Vrhovac, Radovan
AU - Atallah, Ehab
AU - Verstovsek, Srdan
N1 - Funding Information:
Editorial assistance was provided by Maria Vinyll of the Curry Rockefeller Group and funded by Incyte Corporation. Additionally, we would like to thank Dr. Nicholas J. Sarlis, of Incyte Corporation, for stimulating discussions and helpful suggestions.
PY - 2012
Y1 - 2012
N2 - Splenomegaly is a common sign of primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), and post-essential thrombocythemia myelofibrosis (post-ET MF) that is associated with bothersome symptoms, which have a significant negative impact on patients quality of life. It may also be present in patients with advanced polycythemia vera (PV) or essential thrombocythemia (ET). Until recently, none of the therapies used to treat MF were particularly effective in reducing splenomegaly. The discovery of an activating Janus kinase 2 (JAK2) activating mutation (JAK2V617F) that is present in almost all patients with PV and in about 50-60 % of patients with ET and PMF led to the initiation of several trials investigating the clinical effectiveness of various JAK2 (or JAK1/JAK2) inhibitors for the treatment of patients with ET, PV, and MF. Some of these trials have documented significant clinical benefit of JAK inhibitors, particularly in terms of regression of splenomegaly. In November 2011, the US Food and Drug Administration approved the use of the JAK1- and JAK2-selective inhibitor ruxolitinib for the treatment of patients with intermediate or high-risk myelofibrosis, including PMF, post-PV MF, and post-ET MF. This review discusses current therapeutic options for splenomegaly associated with primary or secondary MF and the treatment potential of the JAK inhibitors in this setting.
AB - Splenomegaly is a common sign of primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), and post-essential thrombocythemia myelofibrosis (post-ET MF) that is associated with bothersome symptoms, which have a significant negative impact on patients quality of life. It may also be present in patients with advanced polycythemia vera (PV) or essential thrombocythemia (ET). Until recently, none of the therapies used to treat MF were particularly effective in reducing splenomegaly. The discovery of an activating Janus kinase 2 (JAK2) activating mutation (JAK2V617F) that is present in almost all patients with PV and in about 50-60 % of patients with ET and PMF led to the initiation of several trials investigating the clinical effectiveness of various JAK2 (or JAK1/JAK2) inhibitors for the treatment of patients with ET, PV, and MF. Some of these trials have documented significant clinical benefit of JAK inhibitors, particularly in terms of regression of splenomegaly. In November 2011, the US Food and Drug Administration approved the use of the JAK1- and JAK2-selective inhibitor ruxolitinib for the treatment of patients with intermediate or high-risk myelofibrosis, including PMF, post-PV MF, and post-ET MF. This review discusses current therapeutic options for splenomegaly associated with primary or secondary MF and the treatment potential of the JAK inhibitors in this setting.
KW - JAK2 inhibitor
KW - JAK2V617F mutation
KW - Myelofibrosis
KW - Myeloproliferative neoplasms
KW - Splenomegaly
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U2 - 10.1186/1756-8722-5-43
DO - 10.1186/1756-8722-5-43
M3 - Review article
C2 - 22852872
AN - SCOPUS:84864416539
VL - 5
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
SN - 1756-8722
M1 - 43
ER -