By an integrated clonal reconstruction of AML using cytogenetic, molecular, targeted sequencing, whole exome sequencing and single-cell-derived colony genotyping data, we show that DNMT3A mutations, but also TET2, ASXL1, as well as CBF, MLL and chromosome 20q rearrangements are the first driver events in most AMLs, can persist in remission, and are retained when patients experience relapse. Here, KMT2A is linked to acute myeloid leukemia.