In summary, these data demonstrate that PF-3758309 inhibits oncoproteins frequently deregulated in AML, like c-MYC, and proteins directly deregulated by specific genomic alterations, like DOT1L, in cells with PCAM-MLLT10 rearrangements and FLT3 in cells with FLT3-ITD mutations. Here, DOT1L is linked to acute myeloid leukemia.