To navigate this challenge and investigate new therapeutic opportunities for this aggressive AML subtype, we aimed to find specific dependencies in the context of CBFA2T3::GLIS2 fusion positive AML by interrogating the Broad Institute’s Cancer Dependency Map (DepMap), a data set composed of genome-scale CRISPR-Cas9 screens in over 1 000 cancer cell lines, and by screening additional CBFA2T3::GLIS2 positive AML models. Here, GLIS2 is linked to acute myeloid leukemia.