Model. Loss of PML/RARA DNA binding through RXRA ablation, PML/RARA extinction, or RA/arsenic-triggered catabolism clears target genes from the PML/RARA repressor, triggering differentiation. PML/RARA loss also induces apoptosis. The latter may be blocked by RA, growth factors, or the microenvironment. RARE, RA responsive elements.