While CBFB/MYH11-rearranged leukemias were associated with mutations in RAS-genes, FLT3 and exon 8 frameshift mutations in KIT gene, RUNX1/RUNX1T1-rearranged leukemia correlated with mutations in KIT D816, epigenetic modifiers (ASXL1/2, TET2, IDH2, DNMT3A), cohesion complex components (RAD21, SMC3, SMC1A, STAG2), ZBTB7A, GATA2, JAK2/3 and DHX15. These recurrent mutations likely represent other pathways that are relevant for RUNX1/RUNX1T1-initiated leukemogenesis. The gene discussed is SMC3; the disease is leukemia.