Based on prior investigation of common MLL and AF9 breakpoint regions in AML patient samples [49] and murine models of MA9 [35], we designed guides targeting frequently translocated intronic regions between Mll exons 8 and 9 (Mll sg1 and 2) and exons 10 and 11 (Mll sg3 and 4) and between Af9 exons 8 and 9 (Af9 sg1, 2 and 3) (Figure 1A) to generate two potential MLL-AF9 fusion products (Figure 1B). Here, KMT2A is linked to acute myeloid leukemia.