Mutations in TET2, DNMT3A and NPM1 are thought to be early events in human AML (Jan et al., 2012; The Cancer Genome Atlas Research Network, 2013) and in mouse models mutant Tet2, Dnmt3a and Npm1 cause increased stem cell self-renewal, akin to mutation ‘X’ (Challen et al., 2012; Moran-Crusio et al., 2011; Quivoron et al., 2011; Vassiliou et al., 2011). The gene discussed is NPM1; the disease is acute myeloid leukemia.