Arsenic trioxide (As2O3) is currently being evaluated for treatment of relapsed / refractory disease. Remission with arsenic trioxide has been reported.[15] Studies have shown arsenic reorganizes nuclear bodies and degrades the mutant PML-RAR fusion protein.[16] Arsenic also increases caspase activity which then induces apoptosis.[17] It does reduce the relapse rate for high risk patients.[18] In Japan a synthetic retinoid, tamibarotene, is licensed for use as a treatment for ATRA-resistant APL.[19]