Janus kinase 2 inhibitors in myeloproliferative disorders.
BACKGROUND
JAK2 is an obligatory kinase for the proliferation and differentiation of erythroid cells and megakaryocytes thus representing a relevant therapeutic target for agents that specifically inhibit its activity particularly in myeloproliferative disorders (MPD) harboring JAK2(V617F) mutations.


METHODS
We discuss the physiopathology of the JAK2 signaling pathway and review clinical trials of JAK2 inhibitors for the treatment of MPD using papers and meeting abstracts published up to September 2010.


RESULTS
This review helps in understanding the potential role of JAK2 inhibitors in MPD clinical trials and provides a comprehensive review regarding their efficacy and safety in these disorders.


CONCLUSIONS
JAK2 inhibitors may prove to be useful only for suppressing disease manifestations. However, unlike drugs such as IFN which are capable of eliminating the malignant clone, JAK2 inhibitors are unable to eradicate the disease. In fact, results to date indicate that although these inhibitors reduce splenomegaly and alleviate constitutional symptoms irrespective of JAK2 mutational status, most have only a modest impact on the JAK2(V617F) allele burden. Considering the relevant risk of serious complications in patients undergoing splenectomy, these drugs could find a suitable indication in patients with myelofibrosis awaiting bone marrow transplantation.
Unità Operativa Complessa di Ematologia, Dipartimento di Medicina Interna, Azienda Ospedaliera di Cosenza, Viale della Repubblica, 87100 Cosenza, Italy. fortunato_morabito@tin.it
Eugenio
E
Lucia
Anna Grazia
AG
Recchia
Massimo
M
Gentile
Sabrina
S
Bossio
Ernesto
E
Vigna
Carla
C
Mazzone
Antonio
A
Madeo
Lucio
L
Morabito
Vincenzo
V
Gigliotti
Laura
L
De Stefano
Nadia
N
Caruso
Pasquale
P
Servillo
Stefania
S
Franzese
Maria Grazia
MG
Bisconte
Carlo
C
Gentile
Fortunato
F
Morabito
D000818:Animals; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013163:Splenomegaly / Q000188:drug therapy / Q000209:etiology
D047428:Protein Kinase Inhibitors; D053614:Janus Kinase 2