On the other hand, without PML mutations, APL patients have exhibited no resistance to arsenic trioxide [17], indicating that the binding of As2O3 in the RBCC domain appears to be critical for the effect of arsenic on PML-RARα degradation; more specifically, Cys77/80 and Cys88/91 in the RING domain as well as Cys212 and Cys213 in the B2 domain are found to be arsenic targeting sites [12]. The gene discussed is PML; the disease is acute promyelocytic leukemia.