With efficient knockdown of CNOT3 (Fig. 1E), we observed significant inhibition of growth across a panel of genetically diverse leukemia cell lines including MOLM13 (AML French-American-British classification (FAB) M5a; MLL-AF9 fusion, FLT3-ITD); OCI-AML3 (FAB M4; NPM1 and DNMT3 mutations); NB4 (APL/FAB M3; PML-RARA fusion); HL-60 (FAB M2; c-MYC amplification); NOMO-1 (FAB M5a; MLL-AF9 fusion) and THP-1 (pediatric AML; MLL-AF9 fusion) (Fig. 1F and Supplementary Fig. 1E–I). Here, RUNX2 is linked to acute myeloid leukemia.