To select targets that are likely to exhibit minimal adverse effects and thus have a higher likelihood of success in drug development, we applied a differential essentiality filter to our screen dataset and identified and characterized a potential AML therapeutic target, namely KAT2A. Genetic or pharmacological suppression of KAT2A did not show detectable adverse effects in either mouse HPC-7 hematopoietic precursor cell line or human cord blood CD34+ cells, further supporting that our approach was valid. Here, KAT2A is linked to acute myeloid leukemia.