Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient

Response assessment was evaluated by BM aspirate examination and fluorescence in situ hybridization analysis. The analyses of total arsenic concentrations and speciation were preformed by inductively coupled plasma mass spectrometry (ICP-MS), and high-performance liquid chromatography (HPLC)/ICP-MS, respectively.Response assessment showed that the patient achieved complete remission. The total arsenic concentrations in BM plasma increased with time during the consecutive administration. The PB plasma concentrations of methylated arsenic metabolites substantially increased after the start of administration, while those of inorganic arsenic were still kept at a low level, followed by substantially increase from day-14 after administration. The arsenic speciation profiles of PB plasma were very similar to those of BM plasma. Furthermore, the total arsenic concentrations of HMW-F in BM plasma were much higher than those in PB plasma.The behaviors of arsenic speciation suggested for the first time that arsenic speciation analysis of PB plasma could be predicative for BM speciation, and showed relatively higher efficiency of drug metabolism in the patient. These results may further provide not only significance of clinical application of ATO, but also a new insight into host defense mechanisms in APL patients undergoing ATO treatment, since HMW proteins-bound arsenic complex could be thought to protect BM from the attack of free arsenic species.Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) and accounts for approximately 10-15% of all cases of AML in adults [1]. It is also characterized by a specific cytogenetic reciprocal chromosome translocations, t(15;17), generating PML/RARα fusion gene, which is thought to play a central role in the initiation of leukemogenesis [2-5]. An introduction of all-trans retinoic acid (ATRA) since 1986 has dramatically improved the outcome of treatment of this disease [3]. Nevertheless, an approximatel