Biol. Pharm. Bull. 29(5) 1022—1027 (2006)

in the French–American and British (FAB) classification and represents approximately 5—10% of all leukemia in adults. In about 95—98% of the cases, APL is associated with the reciprocal translocation, t(15; 17)(q22; q21) and the reciprocal fusion of the retinoic acid receptor (RAR)a gene on chromosome 17 with the promyelocytic leukemia (PML) gene on chromosome 15. The resulting PML-RARa fusion gene encodes a chimeric protein that causes the pathogenesis of APL. Huang et al. reported that all-trans retinoic acid (ATRA)—a vitamin A derivative—yielded a high rate of complete remission for APL patients. Several clinical studies have shown that ATRA treatment in combination with chemotherapy induced survival rate of 67—84% at 2—4years. Currently, ATRA has become a first-line treatment of newly diagnosed APL. The combination of ATRA with chemotherapy can obtain long-term survival in 70% of newly diagnosed APL. Nevertheless, the remaining 30% of patients relapse and are often resistant to further treatment with ATRA and chemotherapy. In 1996, the Chinese Shanghai II Medical University Group reported that arsenic trioxide induced apoptosis of APL cells, and 14 of 15 patients who relapsed after ATRA therapy achieved complete remission (CR) with no serious adverse events. Several studies reported that intravenous infusion of arsenic trioxide was effective in approximately 90% of relapsed APL patients who are resistant to ATRA and chemotherapy. However these studies have not accurately investigated the metabolism of arsenic trioxide after the intravenous infusion. In this study, arsenic trioxide was administered intravenously to ATRA-resistant APL patient, and we determined the efficacy of arsenic trioxide in APL as well as the serum or urine concentrations of inorganic arsenic and the methylated metabolites.