Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations.
Most recently, ASXL1, SRSF2, and IDH2 mutations have been associated with inferior overall, leukemia-free or fibrosis-free survival in PV; similarly adverse mutations in ET included SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2.
ASXL1 and SRSF2 mutations have been associated with inferior overall, leukemia-free, or fibrosis-free survival in both PV and PMF, and a recent targeted sequencing study has identified additional other adverse mutations in both these disorders, as well as in ET.
Moreover, significantly more mutated splicing genes (SF3B1, SRSF2 and U2AF1) were present in PMF (0·60 mutated genes/patient) compared to ET (0·15) while no mutations in splicing genes were found in PV.