Using this custom library, we performed pooled CRISPR/Cas9 drop-out screens in two independent AML cell lines and identified the poorly studied F-box protein FBXL6 as the most prominent common dependency between OCI-AML3 (DNMT3A and NMP1 mutated) and MOLM-13 (FLT3-ITD) cells (Fig. 1A, Supplementary Table 1). Here, DNMT3A is linked to acute myeloid leukemia.