Distinct bilineal leukemia immunophenotypes are not genetically determined

We described the association of gain-of-function germline JAK2 mutations (T108A, L393V) coexisting with JAK2V617F in subjects with polycythemia vera phenotype. Both JAK2 germline mutations showed in vitro hypersensitivity to erythropoietin in BaF/3-EPOR cells and weak activation of JAK2/STAT signaling. It is suggestive, that JAK2 germline mutations may provide clonal advantage and increase the probability of acquiring JAK2V617F lesion during the evolution of polycythemia vera phenotype and may contribute to further genomic alterations in polycythemia vera clone and eventually fatal leukemic transformation.