Given that histone H3K79 methylation is associated with active gene transcription (Schübeler et al., 2004), this suggests that DOT1L activity and the altered H3K79 epigenetic signature observed at MLL-FP binding loci may also contribute to the expression of the oncogenic program in MLL-r leukemias (Bernt et al., 2011; Jo et al., 2011; Chen et al., 2013; Deshpande et al., 2013). The gene discussed is KMT2A; the disease is leukemia.