The use of AML cell lines wild-type or mutant for DNMT3A, as well as the generation of isogenic DNMT3A WT/mutant cell line pairs, allowed us to better examine the potential synthetic lethal interaction between DNMT3A and other DNMT family members DNMT1 and DNMT3B. Although studies have reported that DNMT3B is essential for cancer cell growth and survival35–37, we did not identify an essential role for the de novo methyltransferase across any AML cell lines with respect to viability in our CRISPR-based screens. This evidence concerns the gene DNMT3A and cancer.