EZH2 and chronic myelomonocytic leukemia: The genetic heterogeneity of CMML, in patients and in between patients, suggests that the disease has different potential evolutional trajectories.21, 23 Current studies suggest that the preferred order of mutational accumulation is TET2 (or IDH1/2) or ASXL1 (EZH2) first, spliceosome component mutations (SRSF2, SF3B1, U2AF1 or ZRSR2) next, followed by transcription factor mutations (RUNX1) and then signal pathway gene mutations (RAS, CBL), inducing GM-CSF (granulocyte macrophage-colony stimulating factor) hypersensitivity and myeloproliferation (Figure 3).21, 23, 24