Department of Hematology and Rheumatology, Nihon University School of Medicine, Itabashi Hospital, Tokyo, Japan.
J Hematol Oncol. 2012 Jan 24;5:1. doi: 10.1186/1756-8722-5-1.
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.
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.
已经对急性早幼粒细胞白血病（APL）患者外周血（PB）等临床样本中的三氧化二砷（ATO）代谢物进行了形态分析。然而，骨髓（BM）中的砷形态尚未进行分析。因此，研究了 BM 血浆中砷形态的分布，并与复发 APL 患者的 PB 血浆进行了比较。还测定了 BM 和 PB 血浆高分子量部分（HMW-F）中总砷浓度。
通过骨髓抽吸检查和荧光原位杂交分析评估反应。总砷浓度和形态分析分别采用电感耦合等离子体质谱法（ICP-MS）和高效液相色谱/ICP-MS 进行。
反应评估显示患者达到完全缓解。连续给药期间，BM 血浆中的总砷浓度随时间增加。给药开始后，甲基化砷代谢物的 PB 血浆浓度显著增加，而无机砷仍保持在低水平，给药后第 14 天开始显著增加。PB 血浆的砷形态谱与 BM 血浆非常相似。此外，BM 血浆 HMW-F 中的总砷浓度远高于 PB 血浆。
砷形态分析的行为首次表明，PB 血浆中的砷形态分析可以预测 BM 中的砷形态，并且显示出患者对药物代谢的相对较高效率。这些结果不仅可能为 ATO 的临床应用提供意义，而且可能为接受 ATO 治疗的 APL 患者的宿主防御机制提供新的见解，因为 HMW 蛋白结合的砷复合物可以保护 BM 免受游离砷物种的攻击。
