This had led to the theory that residual PU.1 activity is required to promote leukaemogenesis.15 However, an alternative model with somatic Pu.1 deletion causing a complete loss of protein also causes AML,16 and Pu.1 hypomorphic mutants are frequently observed in radiation-induced mouse models of AML.17, 18, 19, 20 This suggests that any loss of PU.1 below a certain threshold may be sufficient for leukaemogenesis;21 however, a recent report suggests that some PU.1 function/levels are needed to maintain stem cell function of leukaemic cells.22 This evidence concerns the gene SPI1 and acute myeloid leukemia.