To confirm the role of the SETD1A SET domain in MLL-r/FLT3-ITD AML, we generated mice with floxed Setd1a exon 17, allowing deletion of the SETD1A S-adenosyl methionine-binding region (Supplementary Fig. 1C), and established a leukemia cell line by transducing retrovirus-based expression vectors for MLL-AF9, FLT3-ITD, and CreERT2 into bone marrow-derived LSK cells (Supplementary Fig. 1C, D). Here, MLLT3 is linked to acute myeloid leukemia.