Another international study of 797 patients with PMF demonstrated the detrimental effect of harboring ≥2 HMR mutations (ASXL1, EZH2, SRSF2, or IDH1/2) with significantly shorter median leukemia-free survival as compared to one HMR mutation only and absence of HMR mutations (2.6, 7, and 12.3 years, respectively) [45]. This evidence concerns the gene IDH1 and leukemia.