In a multinational study of 879 patients with PMF, Vannucchi et al. identified five high molecular risk (HMR) mutations (harbored by 25–30% of the patients with PMF) that affected leukemia-free survival (LFS) and OS (ASXL1, EZH2, IDH1, IDH2, SRSF2) [26]. Here, EZH2 is linked to leukemia.