The analysis of the major genetic events at various stages of leukemia development allowed to propose a model of clonal evolution of CBF AMLs involving an initiating event of inv(16) or t(8;21); at a later stage of leukemia development, additional genetic abnormalities occurs, mainly represented by mutations in driver genes (FLT3, KIT, DNMT3A, SM1CA, SMC3, EZH2, NRAS, WT1, DHX15) or chromosomal abnormalities (trisomy 8, del 6p). The gene discussed is NRAS; the disease is leukemia.