Nucleophosmin-1 (NPM1) mutations in AML not only dislocate NPM1 from the nucleolus but also disorganize the PML nucleosome, ATRA in combination with ATO synergistically induces proteasomal degradation of NPM1 mutations in AML cell lines or primary samples leading to differentiation and apoptosis, and downregulation of the NPM1 mutant by ATRA + ATO also enhances the therapeutic response of AML cells to doxorubicin (El Hajj et al., 2015; Martelli et al., 2015). This evidence concerns the gene NPM1 and acute myeloid leukemia.