(a–d) Four patients harbouring a del(5q) who responded well to lenalidomide treatment. UPN01 (a) shows a linear evolution pattern. In UPN08, 09 and 10 (b–d), non-MDS-related clonal populations increased in frequency under lenalidomide treatment. The MDS clonal populations followed a linear evolution in UPN08 and 09, and a branched evolution in UPN10. (e) Patient with a normal karyotype and without a major response to lenalidomide treatment. This patient shows a branching evolutionary pattern, with a change in clonal composition under 5-azacitidine treatment. 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.