Effects of arsenic on APL cells. (A) Schematic represents the structure of PML, RARα, and PML-RARα. (B) The NB4 cells were treated with 1μM ATO for indicated time points and were assessed by immunofluorescence staining with an anti-PML antibody (green). Stainings were analyzed using a Leica TCS SP5 confocal microscope equipped with a 63×/1.4 NA oil objective (Leica Microsystems). Images were processed using Leica AF lite software. (C) Arsenic induces dual effects on APL cells. The NB4 cells were treated with indicated concentration for 48 hours and stained with the Wright stain. Stainings were analyzed using an Olympus BX51 research microscope equipped with a 100×/1.30 NA oil objective (Olympus). Images were processed using Adobe Photoshop CS (Adobe Systems). Original magnification, ×1000. (D) Colocalization of PML and PML-RARα with the fluorescent organic arsenical ReAsH in NB4 cells. Images were visualized and processed using the equipment described for panel B. (E) The schematic diagram of the structure of PML RING coordinated with zinc or arsenic. (F) Predicted structure of PML RING/UBC9 complex. (G) A working model of the mechanism by which arsenic controls the fate of PML and PML-RARα.