The as yet unfinished story of MPN pathogenesis started with the discovery of the JAK2 (V617F) mutation;[11] afterwards many other mutations have been found in chronic (exon 12 mutations of JAK2, MPL, TET2, LNK, EZH2) and blast phase (NF1, IDH1, IDH2, ASXL1, CBL, Ikaros) of MPN, some involving JAK-STAT signaling activation, others chromatin remodeling and others leukemic transformation. The gene discussed is EZH2; the disease is myeloproliferative disorder.