Mutations in the Pu.1 DNA-binding domain are common in radiation-induced murine leukaemia,19 although not in human AML.47 Within the DNA-binding domain, R235 is highly conserved across species, and structural studies have shown that it has a crucial role in DNA binding at the GGAA core of the Ets motif, leading to the prediction that DNA binding would be impossible in its mutated state.3 Unexpectedly, our ChIP data clearly demonstrate the DNA-binding capacity of this mutant PU.1 protein. Here, SPI1 is linked to acute myeloid leukemia.