Effects of ATO on CyPNs and PML NBs. PML bodies are exported to the cytoplasm and transformed into CyPNs through mitotic cell division. After mitosis, CyPNs contribute to formation of new PML bodies through nuclear import of PML body components. SUMO-conjugates are lost from PML and PML NBs during progression through mitosis, whereas nucleoporins (Nups) are complexed to CyPNs at exit from mitosis. The model depicts 4 different consequences of direct PML and PML/RARA targeting by ATO: (1) inhibition of CyPN dissociation and nuclear import of PML body components after mitosis; (2) stimulation of PML and PML/RARA modifications by SUMOylation and disulphide formation; (3) stimulation of PML and PML/RARA aggregation into PML NBs; and (4) stimulation of RNF4-dependent degradation of PML and PML/RARA by the proteasome within PML NBs. Not shown in this model is the disruption of PML NBs that occur on expression of PML/RARA in APL cells.