Similarly, two independent pooled shRNA screens in primary cells from mouse models of MLL–AF9 acute myeloid leukemia (AML) did not identify DOT1L as an essential enzyme for these tumors [8, 9], even though Dot1l knockout mouse models [10, 11] and a small molecule DOT1L inhibitor [12] have indicated a requirement for DOT1L in MLL-driven AML. The gene discussed is DOT1L; the disease is acute myeloid leukemia.