Given their frequency in myeloid leukemia (Cancer Genome Atlas Research Network, 2013) and the fact that they are not late mutations (Krönke et al., 2013; Shlush et al., 2014), this observation frames NPM1 mutations as “gatekeepers” of leukemogenesis, i.e., their acquisition appears to be closely associated with the development of frank leukemia. Here, NPM1 is linked to myeloid leukemia.