Similar to findings presented here that CRISPR-mediated KO of mtNPM1 repressed HOXA genes and MEIS1, in a recent report the targeted degradation of NPM1c or treatment with selinexor of AML cells, was shown to disrupt the binding of the residual and nuclear NPM1c to exportin-1, which led to repression of a small subset of normal MLL1-regulated genes, including HOXA genes and MEIS1, without affecting MLL1 occupancy at the target loci [19]. The gene discussed is XPO1; the disease is acute myeloid leukemia.