去甲氧柔红霉素和硼替佐米对急性髓系白血病细胞凋亡及钙网蛋白表达的影响

doi:10.3969/j.issn.1671-2587.2019.05.017

临床输血与检验 ›› 2019, Vol. 21 ›› Issue (5): 502-505.DOI: 10.3969/j.issn.1671-2587.2019.05.017

去甲氧柔红霉素和硼替佐米对急性髓系白血病细胞凋亡及钙网蛋白表达的影响

吴金菊, 郭青, 刘欣, 王兴兵, 汪健, 李庆, 沈季敏

230001 合肥,中国科学技术大学第一附属医院（安徽省立医院）血液科

收稿日期:2018-09-12 出版日期:2019-10-20 发布日期:2019-10-29
通讯作者: 刘欣,男,主任医师,主要从事内科血液病基础研究和临床研究,（E-mail） lxinahf@sina.com。
作者简介:吴金菊（1992-）,女,安徽六安人,医师,硕士,主要从事急性白血病与白血病干细胞研究工作,（E-mail）1534986725@qq.com。
基金资助:
*本课题受安徽省自然科学基金项目（No.1508085MH195）资助

The Impact of Bortezomib and Idarubicin Therapy on Calreticulin Expression and Apoptosis of Acute Myeloid Leukmia Cells

WU Jin-ju, GUO Qing, LIU Xin, et al

Department of Hematology, Anhui Provincial Hospital of the University of Science and Technology of China, Hefei 230001

Received:2018-09-12 Online:2019-10-20 Published:2019-10-29

摘要/Abstract

摘要： 目的研究去甲氧柔红霉素（idarubicin ,IDA）、硼替佐米（bortezomibin,BOR）及联合用药对急性髓系白血病（acute myeloid leukemia,AML）不同免疫表型细胞群细胞凋亡及钙网蛋白表达的影响,为寻找有效杀伤白血病细胞的治疗方法提供部分实验依据。方法收集20例初治AML患者外周血,利用淋巴细胞分离液及密度梯度离心法分离出单个核细胞,通过流式细胞术检测CD34⁺CD38⁺细胞群、CD34⁺CD38^-细胞群。用去甲氧柔红霉素和硼替佐米,以指定浓度和时间分别单独或联合作用于初发AML患者外周血单个核细胞,应用流式细胞术检测CD34⁺CD38^-细胞、CD34⁺CD38⁺细胞的凋亡率及细胞表面钙网蛋白的表达,分析两种药物对凋亡率及免疫原性（钙网蛋白表达率）的影响。结果单药处理组间各细胞群凋亡率和钙网蛋白表达率无明显差别,明显低于联合处理组,高于空白组。去甲氧柔红霉素单药组、蛋白酶体抑制剂单药组及两药联合各处理组内CD34⁺CD38⁺细胞凋亡率均高于CD34⁺CD38^-细胞凋亡率[（45.97±7.85）% 对（20.81±1.87）% ,P=0.007;（44.16±6.83）% 对（21.93±4.74）% ,P=0.010;（65.63±7.92）% 对（41.69±3.85）% ,P=0.009],钙网蛋白表达率也有同样表现[（25.31±2.73）% 对（4.40±1.17）% ,P<0.001;（24.27±4.20）% 对（4.27±0.49）% ,P=0.010;（42.13±6.06）% 对（22.06±2.13）%,P=0.006]。结论去甲氧柔红霉素、蛋白酶体抑制剂均能诱导白血病细胞凋亡和凋亡细胞表面钙网蛋白表达,联合用药有协同作用。CD34⁺CD38⁺细胞比CD34⁺CD38^-细胞更易诱导凋亡及表达钙网蛋白。

关键词: 急性髓系白血病, 去甲氧柔红霉素, 蛋白酶体抑制剂, 细胞凋亡

Abstract: Objective To explore the production of calreticulin (CRT) and apoptosis of acute myeloid leukemia cells induced by bortezimib combinated with idarubicin, so as to improve the strategy of leukemia treatments.Methods Peripheral mononucleated cells were isolated by lymphocyte separation and density gradient centrifugation in 20 patients with newly diagnosed AML. The CD34⁺CD38⁺ cells and CD34⁺CD38^- cells were detected by flow cytometry. Under optimal time and concentration, the leukemia cells were treated with bortezimib or idarubicin alone or in combination of the both, and the apoptosis and CRT expression on CD34⁺CD38⁺ and CD34⁺CD38^- cells were analyzed.Results No significant difference of the apoptotic rate of the cells and expression level of CRT was observed between the bortezimib and idarubicin treatments but combination of the both agents significantly ameliorated the cell injuries. Additionally, the apoptosis were more deteriorated in CD34⁺CD38⁺ cells compared with CD34⁺CD38^- cells in idarubicin (P=0.007),bortezimib (P=0.01) and idarubicin+Bortezimib treatments (P=0.009）. Similar results were seen in CRT expression (P=0.000, P=0.01, and P=0.006).ConclusionIdarubicin and proteasome inhibitors may induce apoptosis and increase the expression of calreticulin on leukemic cells, particularly of CD34⁺CD38⁺ cells, and combination therapy is synergistically effective.

Key words: Acute myeloid leukemia, Idarubicin, Bortezomib, Apoptosis

中图分类号:

R733.71 R446.6

吴金菊, 郭青, 刘欣, 王兴兵, 汪健, 李庆, 沈季敏. 去甲氧柔红霉素和硼替佐米对急性髓系白血病细胞凋亡及钙网蛋白表达的影响[J]. 临床输血与检验, 2019, 21(5): 502-505.

WU Jin-ju, GUO Qing, LIU Xin, et al. The Impact of Bortezomib and Idarubicin Therapy on Calreticulin Expression and Apoptosis of Acute Myeloid Leukmia Cells[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2019, 21(5): 502-505.

参考文献

1 Estey E. Acute myeloid leukemia: 2016 Update on risk-stratification and management[Z]. 2016:91, 824-846.
2 Blum S, Martins F, Lubbert M. Immunotherapy in adult acute leukemia[J]. Leuk Res,2017,60:63-73.
3 Lichtenegger F S, Krupka C, Haubner S, et al. Recent developments in immunotherapy of acute myeloid leukemia[J]. J Hematol Oncol,2017,10(1):142.
4 Romaniuk W,Oldziej A E,Zinczuk J,et al. [Proteasome inhibitors in cancer therapy][J]. Postepy Hig Med Dosw (Online), 2015,69:1443-1450.
5 Xu L,Luo J,Jin R,et al. Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption[J]. Mol Cancer Ther, 2016,15(5):854-865.
6 Terwijn M,Zeijlemaker W,Kelder A,et al. Leukemic stem cell frequency: a strong biomarker for clinical outcome in acute myeloid leukemia[J]. PLoS One, 2014,9(9):e107587.
7 Wouters R,Cucchi D,Kaspers G J,et al. Relevance of leukemic stem cells in acute myeloid leukemia: heterogeneity and influence on disease monitoring, prognosis and treatment design[J]. Expert Rev Hematol, 2014,7(6):791-805.
8 张翠萍,魏辉,王慧君,等. 初诊急性髓系白血病骨髓CD34~+ CD38~-细胞群比例是初次诱导缓解率的预后因素[J]. 中国实验血液学杂志,2011,19(5):1268-1272.
9 Witte K E,Ahlers J,Schafer I,et al. High proportion of leukemic stem cells at diagnosis is correlated with unfavorable prognosis in childhood acute myeloid leukemia[J]. Pediatr Hematol Oncol,2011,28(2):91-99.
10 Obeid M,Tesniere A,Ghiringhelli F, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death[J]. Nat Med,2007,13(1):54-61.
11 Loke J,Khan J N,Wilson J S,et al. Mylotarg has potent anti-leukaemic effect: a systematic review and meta-analysis of anti-CD33 antibody treatment in acute myeloid leukaemia[J]. Ann Hematol,2015,94(3):361-373.
12 Kantarjian H M,Shah N P,Cortes J E, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia[J]. Blood,2015,119(5):1123.
13 Janakiram M, Pareek V,Cheng H, et al. Immune checkpoint blockade in human cancer therapy: lung cancer and hematologic malignancies[J]. Immunotherapy,2016,8(7):809-819.
14 Zhang Q,Liu X,Wang X B,et al. [Amplification Ex Vivo and Cytocidal Activity of Leukemia Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes][J]. 中国实验血液学杂志,2015,23(3):814-820.
15 Srivastava,Shivani,Riddell,et al. Engineering CAR-T Cells: Design Concepts.[J]. Trends in Immunol, 2015,36(8):494.

[1]	吴月, 朱小玉, 刘会兰, 宋闿迪, 汤宝林, 孙自敏. 强化清髓单份非血缘脐血移植治疗FLT3-ITD突变阳性急性髓系白血病疗效观察^*[J]. 临床输血与检验, 2020, 22(6): 627-632.
[2]	张涛, 谭茜茜, 廖红梅, 刘不尽, 李浏卿, 芸邹, 晓萍, 欧阳熊妍, 毛伟, 兰炯采. 中医药在细胞凋亡中的作用以及对输血治疗的影响[J]. 临床输血与检验, 2019, 21(3): 248-251.
[3]	孟强, 宋敏, 赵树铭, 范娅涵. 红细胞贮存损伤的生化和组学变化研究进展^*[J]. 临床输血与检验, 2018, 20(6): 672-676.
[4]	盛佳佳, 刘雨生. 曲古菌素A联合全反式维甲酸诱导卵巢癌SK0V-3细胞株凋亡的研究[J]. 临床输血与检验, 2017, 19(4): 321-324.
[5]	刘春秋, 卞茂红. 药物致红细胞凋亡的研究进展^*[J]. 临床输血与检验, 2017, 19(4): 409-413.

去甲氧柔红霉素和硼替佐米对急性髓系白血病细胞凋亡及钙网蛋白表达的影响

The Impact of Bortezomib and Idarubicin Therapy on Calreticulin Expression and Apoptosis of Acute Myeloid Leukmia Cells

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 5

编辑推荐

Metrics

本文评价

关于本刊

作者中心

在线期刊

访问统计

联系我们