Article

Janus kinase 2 inhibitors in myeloproliferative disorders.

Unità Operativa Complessa di Ematologia, Dipartimento di Medicina Interna, Azienda Ospedaliera di Cosenza, Viale della Repubblica, 87100 Cosenza, Italy.
Expert Opinion on Investigational Drugs (impact factor: 5.27). 01/2011; 20(1):41-59. DOI:10.1517/13543784.2011.538382 pp.41-59
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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Keywords

agents
 
bone marrow transplantation
 
comprehensive review
 
drugs
 
efficacy
 
erythroid cells
 
JAK2 inhibitors
 
JAK2 mutational status
 
JAK2 signaling pathway
 
malignant clone
 
MPD clinical trials
 
obligatory kinase
 
patients undergoing splenectomy
 
relevant risk
 
relevant therapeutic target
 
review clinical trials
 
serious complications
 
splenomegaly
 
suitable indication
 
suppressing disease manifestations