切换至 "中华医学电子期刊资源库"
高级检索
中华危重症医学杂志(电子版)

中华危重症医学杂志(电子版) ›› 2017, Vol. 10 ›› Issue (03) : 165 -171. doi: 10.3877/cma.j.issn.1674-6880.2017.03.005

所属专题： 文献；

论著

急性髓样白血病患者骨髓干细胞CD200的表达及与临床疗效的关系
胡蓓莉1, 张隽瑜2, 贺超奇3, 童向民4,†()   
  1. 1. 314000　浙江嘉兴，嘉兴市第二医院血液科
    2. 323000　浙江丽水，丽水市中心医院血液科
    3. 311200　杭州，杭州市萧山区第一人民医院检验科
    4. 310003　杭州，浙江大学医学院附属第一医院血液科
  • 收稿日期:2016-10-09 出版日期:2017-06-01
  • 通信作者: 童向民
  • 基金资助:
    国家自然科学基金项目(81570198); 杭州市科技局项目(20140633B50)

Expression of CD200 in acute myeloid leukemia bone marrow stem cells and its clinical efficacy

Beili Hu1, Junyu Zhang2, Chaoqi He3, Xiangmin Tong4,†()   

  1. 1. Departmant of Hematology, Jiaxing Second Hospital, Jiaxing 314000, China
    2. Departmant of Hematology, Lishui Central Hospital, Lishui 323000, China
    3. Departmant of Laboratory Medicine, the First People's Hospital of Xiaoshan District, Hangzhou 311200, China
    4. Departmant of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
  • Received:2016-10-09 Published:2017-06-01
  • Corresponding author: Xiangmin Tong
  • About author:
    Corresponding author: Tong Xiangmin, Email: tongxiangmin@163.com
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

胡蓓莉, 张隽瑜, 贺超奇, 童向民. 急性髓样白血病患者骨髓干细胞CD200的表达及与临床疗效的关系[J]. 中华危重症医学杂志(电子版), 2017, 10(03): 165-171.

Beili Hu, Junyu Zhang, Chaoqi He, Xiangmin Tong. Expression of CD200 in acute myeloid leukemia bone marrow stem cells and its clinical efficacy[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2017, 10(03): 165-171.

目的

研究急性髓样白血病（AML）患者骨髓中CD200的表达情况及与临床疗效关系的相关研究。

方法

将51例急性髓样白血病患者根据初发时白细胞计数分为高白细胞组（18例）与非高白细胞组（33例），根据化疗效果分为完全缓解组（31例）和未缓解组（20例），同期选取51例缺铁性贫血或巨幼细胞贫血患者为对照组。采用流式细胞术检测AML患者化疗前后CD200、Foxp3+/CD4+的表达，酶联免疫吸附试验检测AML患者及对照组患者外周血白细胞介素17（IL-17）、IL-4和干扰素γ的水平。同时，采用Pearson线性相关分析研究AML患者中CD200表达水平与化疗前后血清IL-17、IL-4、干扰素γ水平及骨髓中Foxp3+/CD4+水平的关系。

结果

高白细胞组患者CD200阳性表达率明显高于非高白细胞组患者[（4.8 ± 2.8）% vs.（3.7 ± 2.2）%，t = 4.961，P < 0.001]。未缓解组患者较完全缓解组患者明显偏高[（4.8 ± 2.6）% vs.（3.1 ± 1.6）%，t = 5.716，P < 0.001]。对照组患者与AML患者化疗前比较，IL-17及干扰素γ水平均明显升高（t = 26.970，P < 0.001；t = 4.370，P < 0.001），IL-4水平及Foxp3+/CD4+细胞均明显降低（t = 9.965，P < 0.001；t = 7.346，P < 0.001）。而对照组患者与AML患者化疗后比较，仅IL-17及IL-4水平比较，差异有统计学意义（t = 8.897，P < 0.001；t = 3.965，P < 0.001）。与AML患者化疗前比较，化疗后IL-17 [（147 ± 42）ng/L vs.（332 ± 68）ng/L，t = 15.920，P < 0.001]及干扰素γ [（24 ± 8）μg/L vs.（31 ± 12）μg/L，t = 3.576，P < 0.001]水平均明显升高，IL-4水平[（142 ± 54）μg/L vs.（84 ± 31）μg/L，t = 6.644，P < 0.001]及Foxp3+/CD4+细胞[（7.5 ± 2.4）% vs.（5.2 ± 2.4）%，t = 5.330，P < 0.001]均明显降低。Pearson线性相关分析发现，CD200表达水平仅与化疗后骨髓中Foxp3+/CD4+水平呈正相关（r = 0.347，P = 0.012）。

结论

CD200可能通过抑制免疫相关因子影响AML患者临床疗效。

关键词: 白血病，髓样，急性, 骨髓, 干细胞, CD200, 临床疗效
Objective

To study the expression of CD200 in acute myeloid leukemia (AML) bone marrow stem cells and its clinical efficacy.

Methords

Totally 51 AML patients were divided into the high white blood cell group (18 cases) and non-high white blood cell group (33 cases) according to whether the initial white blood cell count > 100 × 109/L. The 51 AML patients also were divided into the complete response group (31 cases) and the non-response group (20 cases) after the first chemotherapy, and 51 iron-deficiency anemia or megaloblastic anemia patients were selected as the control group at the same time. The expression of CD200 and Foxp3+/CD4+ before and after the first chemotherapy were detected by flow cytometry in AML patients. The levels of interleukin-17 (IL-17), IL-4 and interferon-gamma (IFN-γ) in the peripheral blood before and after chemotherapy were detected by enzyme-linked immunosorbent assay (ELISA) in AML patients and control group. The Pearson correlation was used to analyze the relationship between expression of CD200 in AML patients and IL-17, IL-4, IFN-γ and Foxp3+/CD4+ before and after chemotherapy.

Results

The positive rate of CD200 in the high white blood cell group were much higher than those in the non-high white blood cell group [(4.8 ± 2.8)% vs. (3.7 ± 2.2)%, t = 4.961, P < 0.001], and the positive rate of CD200 in the non-response group also increased as compared with the complete response group [(4.8 ± 2.6)% vs. (3.1 ± 1.6)%, t = 5.716, P < 0.001]. In the control group, the levels of IL-17 and IFN-γ were significantly higher (t = 26.970, P < 0.001; t = 4.370, P < 0.001), the IL-4 and Foxp3+/CD4+ were much lower (t = 9.965, P < 0.001; t = 7.346, P < 0.001) than those in AML patients before chemotherapy. And statistically significant differences were observed only in the levels of IL-17 and IL-4 between the control group and AML patients after chemotherapy (t = 8.897, P < 0.001; t = 3.965, P < 0.001). Compared with the AML patients before chemotherapy, the IL-17 [(147 ± 42) ng/L vs. (332 ± 68) ng/L, t = 15.920, P < 0.001] and IFN-γ [(24 ± 8) μg/L vs. (31 ± 12) μg/L, t = 3.576, P < 0.001] increased markedly, the IL-4 [(142 ± 54) μg/L vs. (84 ± 31) μg/L, t = 6.644, P < 0.001] and Foxp3+/CD4+ [(7.5 ± 2.4)% vs. (5.2 ± 2.4)%, t = 5.330, P < 0.001] decreased obviously after chemotherapy. The expression of CD200 in AML patients was only correlated with Foxp3+/CD4+ levels after chemotherapy (r = 0.347, P = 0.012).

Conclusion

The espression of CD200 can affect the clinical efficacy in AML patients by suppressing the immune-related factors.

Key words: Leukemia, myeloid, acute, Bone marrow, Stem cells, CD200, Clinical efficacy
图1 CD45+/-CD34+CD38-急性髓样白血病-LSCs中CD200+表达情况。注：AML：急性髓样白血病（acute myeloid leukemia）；LSCs：白血病干细胞（leukemia stem cells）
表1 AML患者化疗前后血清IL-17、IL-4及干扰素γ与骨髓AML患者Foxp3+/CD4+水平的变化（ ± s）
组别 例数 IL-17（ng/L） IL-4（μg/L） 干扰素γ（μg/L） Foxp3+/CD4+（%）
化疗前 51 147 ± 42 142 ± 54 24 ± 8 7.5 ± 2.4
化疗后 51 332 ± 68 84 ± 31 31 ± 12 5.2 ± 2.4
t值 ? 15.920 6.644 3.576 5.330
P值 ? <0.001 <0.001 <0.001 <0.001
1
张晓录，沈安俐，郭睿，等. CD200在急性髓细胞白血病中的表达特点及其临床意义[J]. 中国实验血液学杂志，2014，22(6):1531-1534.
2
Damiani D, Tiribelli M, Raspadori D, et al. Clinical impact of CD200 expression in patients with acute myeloid leukemia and correlation with other molecular prognostic factors[J]. Oncotarget, 2015, 6(30): 30212-30221.
3
Lauzon-Joset JF, Langlois A, Lai LJ, et al. Lung CD200 receptor activation abrogates airway hyperresponsiveness in experimental asthma[J]. Am J Respir Cell Mol Biol, 2015, 53 (2): 276-284.
4
Kawasaki BT, Farrar WL. Cancer stem cells, CD200 and immunoevasion[J]. Trends Immunol, 2008, 29 (10): 464-468.
5
Alapat D, Coviello-Malle J, Owens R, et al. Diagn-ostic usefulness and prognostic impact of CD200 expression in lymphoid malignancies and plasma cell myeloma[J]. Am J Clin Pathol, 2012, 137 (1): 93-100.
6
Tonks A, Hills R, White P, et al. CD200 as a pro-gnostic factor in acute myeloid leukaemia[J]. Leukemia, 2007, 21 (3): 566-568.
7
Moreaux J, Hose D, Reme T, et al. CD200 is a new prognostic factor in multiple myeloma[J]. Blood, 2006, 108 (13): 4194-4197.
8
陈永斌，张敏珍，杨国辉. 细胞免疫功能测定在危重症患者中的临床意义[J/CD]. 中华危重症医学杂志（电子版），2010，3(6):384-388.
9
Coles SJ, Wang EC, Man S, et al. CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia[J]. Leukemia, 2011, 25 (5): 792-799.
10
Memarian A, Nourizadeh M, Masoumi F, et al. Upr-egulation of CD200 is associated with Foxp3+ regulatory T cell expansion and disease progression in acute myeloid leukemia[J]. Tumour Biol, 2013, 34 (1): 531-542.
11
Imola M, Mianulli AM, Pasini G, et al. Emergency hemicolectomy for intestinal primary aspergillosis in acute myeloid leukemia[J]. G Chir, 2012, 33 (3): 74-76.
12
Fonseka M, Ramasamy R, Tan BC, et al. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) inhibit the proliferation of K562 (human erythromyeloblastoid leukaemic cell line)[J]. Cell Biol Int, 2012, 36 (9): 793-801.
13
Chen CC, Yang CF, Yang MH, et al. Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia[J]. Ann Oncol, 2005, 16 (8): 1366-1373.
14
范艳莹，吴长有. IL-4、IL-10和抗IL-12受体β1mAb抑制IL-23诱导正常人记忆T细胞IFN-γ产生[J]. 免疫学杂志，2006，22(4):353-357.
15
Guo H, Qiao Z, Zhu L, et al. Th1/Th2 cytokine profiles and their relationship to clinical features in patients following nonmyeloablative allogeneic stem cell transplantation[J]. Am J Hematol, 2004, 7 5(2): 78-83.
16
Harrington LE, Hatton RD, Mangan PR, et al. Int-erleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages[J]. Nat Immunol, 2005, 6 (11): 1123-1132.
17
Sakaguchi S, Sakaguchi N, Asano M, et al. Imm-unologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J]. J Immunol, 1995, 155 (3): 1151-1164.
18
Gorczynski RM, Lee L, Boudakov I. Augmented in-duction of CD4+CD25+ Treg using monoclonal antibodies to CD200R[J]. Transplantation, 2005, 79 (4): 488-491.
19
Shenghui Z, Yixiang H, Jianbo W, et al. Elevated frequencies of CD4+CD25+CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia[J]. Int J Cancer, 2011, 129 (6): 1373-1381.
20
龚晓成，曾辉，韩伟. 胃癌患者外周血CD4+CD25+Foxp3+调节性T细胞55例分析[J/CD]. 中华危重症医学杂志（电子版），2013，6(5):307-309.
21
Beyer M, Schultze JL. Regulatory T cells: major players in the tumor microenvironment.[J]. Curr Pharm Des, 2009, 15 (16): 1879-1892.
[1] 庄蕙嘉, 岳志成, 钟坤岑, 朱慧莉. 乳腺癌患者生育力保存的研究进展[J]. 中华乳腺病杂志(电子版), 2023, 17(04): 238-242.
[2] 卫杨文祥, 黄浩然, 刘予豪, 陈镇秋, 王海彬, 周驰. 股骨头坏死细胞治疗的前景和挑战[J]. 中华关节外科杂志(电子版), 2023, 17(05): 694-700.
[3] 韩李念, 王君. 放射性皮肤损伤治疗的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 533-537.
[4] 张华, 孙宇, 乡世健, 李樱媚, 王小群. 循环肿瘤细胞预测晚期胃肠癌患者化疗药物敏感性的研究[J]. 中华普通外科学文献(电子版), 2023, 17(06): 422-425.
[5] 陈瑜, 尤良顺, 孟海涛, 杨敏. 嵌合抗原受体T细胞治疗多发性骨髓瘤新进展[J]. 中华移植杂志(电子版), 2023, 17(05): 313-320.
[6] 孔欣, 宋宝全, 刘吟, 张剑, 仇惠英, 吴德沛. 异基因造血干细胞移植并发难治性呃逆一例[J]. 中华移植杂志(电子版), 2023, 17(04): 253-255.
[7] 唐英俊, 李华娟, 王赛妮, 徐旺, 刘峰, 李羲, 郝新宝, 黄华萍. 人脐带间充质干细胞治疗COPD小鼠及机制分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 476-480.
[8] 李晔, 何洁, 胡锦秀, 王金祥, 田川, 潘杭, 陈梦蝶, 赵晓娟, 叶丽, 张敏, 潘兴华. 高活性间充质干细胞干预猕猴卵巢衰老的研究[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 210-219.
[9] 龙慧玲, 林蜜, 邵婷. 三维球体间充质干细胞培养技术的研究进展及其应用[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 229-234.
[10] 梁文龙, 曹杰, 黄庆, 林泳, 黄红丽, 杨平, 李冠炜, 胡鹤. 信迪利单抗联合瑞戈非尼治疗晚期结直肠癌的疗效与安全性分析[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 409-413.
[11] 姜里蛟, 张峰, 周玉萍. 多学科诊疗模式救治老年急性非静脉曲张性上消化道大出血患者的临床观察[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 520-524.
[12] 张景旭, 李德舫, 由上可, 张玉田. 贝伐珠单抗与安罗替尼联合奥沙利铂治疗晚期直肠癌的临床疗效[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 289-293.
[13] 盛静, 梅勇, 夏佩, 王晓林. 乌苯美司联合伊立替康二线治疗晚期胃癌的临床研究[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 317-321.
[14] 李莹倩, 李华山. 基于真实世界的完全性直肠脱垂治疗方式评价[J]. 中华临床医师杂志(电子版), 2023, 17(06): 700-705.
[15] 梁宇同, 丁旭, 马国慧, 黄艳红. 间充质干细胞在宫腔粘连治疗中的研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(05): 596-599.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号