三氧化二砷治疗慢性粒细胞性白血病的实验与临床研究

石茵; 向谱; 黄昊; 林全德; 房佰俊

doi:10.13201/j.issn.1004-2806.2017.01.007

三氧化二砷治疗慢性粒细胞性白血病的实验与临床研究

- 1. 中国医学科学院北京协和医学院血液学研究所血液病医院(天津, 300020);
- 2. 郑州大学附属肿瘤医院、河南省肿瘤医院血液科
基金项目:
国家自然科学基金（No：81370661）

详细信息

通讯作者: 房佰俊,E-mail:fdation@126.com

中图分类号: R733.72

收稿日期: 2016-10-14

Clinical and experimental studies on arsenic trioxide in the treatment of chronic myeloid leukemia

- 1. Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College, Tianjin, 300020, China;
- 2. Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Henan Tumor Hospital

More Information

Corresponding author: FANG Baijun, E-mail: fdation@126.com

Received Date: 14 October 2016

摘要

摘要: 目的：观察三氧化二砷（As₂O₃）对免疫表型FIK1⁺CD34^-的慢性粒细胞白血病（CML）干细胞增殖的影响，并初步探讨As₂O₃使CML患者能中断酪氨酸激酶抑制剂治疗的可行性。方法：分离CML患者骨髓细胞中FIK1⁺CD34^-CML干细胞，检测As₂O₃对其细胞周期、凋亡及P53基因表达的影响，并观察应用伊马替尼后已获得完全细胞遗传学缓解的CML患者，单用As₂O₃注射液6周期后，其疗效及不良反应。结果：As₂O₃能抑制免疫表型为FIK1⁺CD34^-的CML干细胞增殖（P<0.05），可使其G0/G1期增加，S期降低，并可诱导凋亡。FIK1⁺CD34^-CML干细胞经适当浓度的As₂O₃处理后，P53基因表达可显著提高。6例患者单用As₂O₃仍保持完全细胞遗传学缓解，且不良反应轻微，经对症处理后均可缓解。结论：As₂O₃对CML患者的治疗有一定效果，且无明显毒副作用，为使CML患者能中断酪氨酸激酶抑制剂的治疗提供了新的研究方向。
- 白血病,粒细胞,慢性 /
- 三氧化二砷 /
- 化疗 /
- 初步研究
Abstract: Objective: To observe the effect of ATO on the proliferation of FIK1⁺CD34^-chronic myeloid leukemia (CML) stem cells,and determine whether ATO alone could maintain remissions achieved by a prior therapy with tyrosine kinase inhibitor.Method: We isolated FIK1⁺CD34^-CML stem cells from the bone marrow of newly diagnosed CML and analyzed the effect of ATO on cell cycle,apoptosis and the gene expression of P53 in FIK1⁺CD34^-CML stem cells.We observed remission status and adverse events of ATO used alone in 6 patients who had been pretreated with imatinib and got complete cytogenetic response.Result: ATO could inhibit the proliferation of FIK1⁺CD34^-CML stem cells.After treatment with ATO,the cells in G0/G1 phase increased and those in S phase decreased.Furthermore,ATO could induce apoptosis of FIK1⁺CD34^-CML stem cells and increase remarkably the expression of P53 gene.After the application of ATO for 6 cycles,all the 6 patients remained complete cytogenetic remission.Furthermore,all the adverse events were modest and responded to symptomatic treatment.Conclusion: Treatment with ATO in patients with CML may have a good result without obvious ATO-related toxicities,and it gives a new way to cure CML without tyrosine kinase inhibitor.
- chronic myeloid leukemia /
- arsenic trioxide /
- chemotherapy /
- preliminary study

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