[Mutation of protein kinase JAK2 in polycythemia vera: new perspectives in physiopathology and therapy]

The pathogenic mechanisms of polyvythemia vera (PV) still remain unknown, although there is evidence that genetic parameters may play a role in the pathogenesis of the disease.

In 2005, many international research groups have identified an acquired mutation in the Janus kinase (JAK2) gene of chromosome 9; the mutation is defined by a valine-to-phenylalanine substitution at amino acid position 617 (V617F) in the JAK2's pseudokinase domain. JAK2 V617F mutation has been found in as high as 65 to 97% of patients with PV. Both in vitro and in vivo functional studies have further indicated that JAK2 V617F mutation leads to dysregulation of kinase activity, explaining, in part, clinical and biochemical features of PV.

These data suggest that JAK2 V617F mutation may be a novel diagnostic marker of PV. Moreover, JAK2 V617F mutation finding may permit promising therapeutic approaches in patients with PV, particularly tyrosine kinase inhibitors; preliminary series have, in fact, underscored the potential efficacy of imatinib mesylate in PV.