To unravel the underlying mechanism of RUNX1’s indispensable role in CBFB-MYH11–induced leukemia (18), we conducted an integrated analysis of the leukemogenicity of CBFB-MYH11 and two CBFB-MYH11 mutations, deletion of the RUNX1 high-affinity binding domain (CBFB-MYH11-ΔHABD) and mutation in the C-terminal multimerization domain (CBFB-MYH11-mDE), and investigated their effects on RUNX1’s functions. The gene discussed is RUNX1; the disease is leukemia.