Polycythemia vera is not initiated by JAK2V617F mutation

Our studies correlating the frequency of JAK2V617F mutant allele and clonality, as well as the presence of homozygous wild-type JAK2 erythropoietin-independent erythroid colonies, provide compelling evidence that the JAK2V617F is not the PV-initiating mutation. This supports a model wherein the JAK2V617F mutation arises as a secondary genetic event. Furthermore, our results indicate that an undefined molecular lesion, preceding JAK2V617F, is responsible for clonal hematopoiesis in PV. We conclude that development of therapeutic strategies that target the JAK2V617F clonal cells may not be sufficient for eradication of PV.