Initiating mutations at low variant allelic frequency (VAF), so called “passenger lesions” (including TET2, DNMT3A, GNAS, ASXL1, SF3B1, PPM1D) usually occur early in the disease course and are not sufficient to cause AML per se [2,6,7,8,9,10]. Here, DNMT3A is linked to acute myeloid leukemia.