title: Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient.
abstract: BACKGROUND
  Speciation of arsenic trioxide (ATO) metabolites in clinical samples such as peripheral blood (PB) from acute promyelocytic leukemia (APL) patients has been conducted. However, speciation of arsenicals in bone marrow (BM) has not yet been performed. Profiles of arsenic speciation in plasma of BM were thus investigated and compared with those of PB plasma from a relapsed APL patient. The total arsenic concentrations in high molecular weight fraction (HMW-F) of BM and PB plasma were also determined.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology and Rheumatology, Nihon University School of Medicine, Itabashi Hospital, Tokyo, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Iriyama
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yoshino
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.forename: Akira
authors.initials: A
authors.lastname: Horikoshi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hatta
authors.forename: Hiroo
authors.initials: H
authors.lastname: Toyoda
authors.forename: Jin
authors.initials: J
authors.lastname: Takeuchi
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001853:Bone Marrow / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism*; D013058:Mass Spectrometry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D010087:Oxides / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011379:Prognosis; D012074:Remission Induction; D016879:Salvage Therapy; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide