NRAS and Increased total leukocyte count: In both cases, concomitant with the emergence and expansion of a clone harbouring a mutation in NRAS, the patient developed leukocytosis (both >100 × 109/l, for UPN06 after the last time point) and progression of disease: UPN11 progressed from RCMD (refractory cytopenia with multilineage dysplasia) to RAEB-1 (refractory anaemia with excess blasts-1) and ultimately developed secondary AML (sAML) (Fig. 2b), whereas UPN06 progressed from RARS (refractory anaemia with ringed sideroblasts) towards RAEB-2 (Fig. 2c).