As shown in Fig. 3, the three most prevalent evolutionary routes characterizing AML SNV Evolutionary Signature (AML SNV Evo Sig) #1 involve alterations in IDH1/2, RAD21, DNMT3A and KIT genes as early evolutionary steps, with later acquisition of TET2 alterations (Fig. 3 and Supplementary Fig. 16). This evidence concerns the gene RAD21 and acute myeloid leukemia.