In MLL-FP leukemias, DOT1L directly interacts with AF9 or ENL (Biswas et al., 2011, Mueller et al., 2007), and can be mis-targeted to MLL-FP-bound genes where it is associated with inappropriate activation of gene expression (Milne et al., 2005) (Figure 1B). The gene discussed is KMT2A; the disease is leukemia.