(a) Patient with one single MDS clone without clonal evolution during the 8 years of follow-up. (b,c) Two patients showing linear clonal evolution. In both cases, a heterozygous NRAS mutation was acquired (green clones), associated with increased leukocyte levels and disease progression. (d–f) Patients with a more complex branching clonal evolution pattern. Vertical dashed lines indicate the investigated sampling moments. The samples indicated with a triangle were analysed by WES. Subsequently, all samples were analysed with targeted deep sequencing. Only important genetic aberrations are indicated; a full list of genetic aberrations can be found in Supplementary Figs 3 and 4, Supplementary Table 3 and Supplementary Data 1 and 2. PCD, pentoxifylline, ciprofloxacin and dexamethasone; tipi+bortezo, tipifarnib and bortezomib.