How does a single JAK2 mutation give rise to different phenotypes and diseases?
These data raise the intriguing question of how a single mutation might give rise to at least three different diseases (PV, ET and IMF) and also to some other atypical MPDs. Evidence from clinical, biological and pathology data indicates that ET, PV and IMF are related disorders. The evolution of ET to PV has been well documented, although some authors have stated these ET patients have been falsely diagnosed and represent in reality a forme fruste of PV. About 15% of ET patients progress to myelofibrosis and approximately 20% of PV progress to IMF (spent phase).39 The boundaries between IMF and ET are not well defined during the so-called pre-fibrotic form of IMF.40 In addition, biological features of PV, i.e., EEC, high PRV1 mRNA in granulocytes are also found in ET and IMF,41 while diminished membrane expression of Mpl (TpoR) by platelets has also been described in ET and IMF.24 Recent results suggest that these criteria except Mpl expression correlate with the JAK2 V617F mutation.
