骨髓增生异常综合征造血细胞bcl-2 VEGF抗原表达及原位凋亡的研究

邱志祥; 李挺; 岑溪南; 许尉林; 任汉云

doi:10.3969/j.issn.1000-8179.2012.11.001

骨髓增生异常综合征造血细胞bcl-2 VEGF抗原表达及原位凋亡的研究

doi: 10.3969/j.issn.1000-8179.2012.11.001

邱志祥^①,
李挺^②,
岑溪南^①,
许尉林^①,
任汉云^①, ,

①.
北京大学第一医院血液内科
②.
病理科（北京市100034）

详细信息

通讯作者:
任汉云 renhy0813@163.com

计量
- 文章访问数: 40
- HTML全文浏览量: 21
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2011-11-14
- 修回日期: 2012-02-06

Investigation of bcl-2 and VEGF Antigen Expression and In Situ Apoptosis of Hematopoietic Cells in Myelodysplastic Syndrome

Zhixiang QIU^①,
Ting LI^②,
Xinan CEN^①,
Weilin XU^①,
Hanyun REN^{①
, ,}

①.
Department of Hematology, The First Hospital of Beijing University, Beijing 100034, China
②.
Department of Pathology, The First Hospital of Beijing University, Beijing 100034, China

More Information

Corresponding author: Hanyun REN; E-mail: renhy0813@163.com

摘要

摘要: 目的研究骨髓增生异常综合征(MDS)bcl-2、VEGF抗原表达及造血细胞原位凋亡之间的关系, 探讨MDS发病机理。方法对MDS患者骨髓活检标本光镜下观察骨髓增生程度、各系造血细胞形态异常情况、不成熟前体细胞异常定位(ALJP)等组织病理学改变, 免疫组织化学染色观测bcl-2及VEGF抗原的表达, TUNEL法检测造血细胞原位凋亡。结果 13例患者骨髓均有不同程度的异常造血, 异常造血主要累及的细胞系列不尽相同, RA、RAEB两组患者异常造血未见明显区别; 有6例患者检出ALIP现象, 其中RA 3例(3/8, 37.50%), RAEB 3例(3/5, 60.00%); VEGF阳性者占9例(9/13, 69.23%), 其中RA 6例(6/8, 75.00%), RAEB 3例(3/5, 60.00%); bcl-2阳性者占7例, 其中RA4例(4/8, 50.00%), RAEB 3例(3/5, 60.00%); TUNEL检测13例患者均为阳性, 检出ALIP现象者, 其造血细胞发生原位调亡明显, 而bcl-2、VEGF与TUNEL结果之间未见明显关联。结论 MDS患者均存在不同程度的细胞凋亡异常, 而TUNEL法提供了简便、实用、敏感、快速特异的检测MDS细胞原位凋亡的方法结果初步显示MDS患者ALlP现象明显者其细胞凋亡也明显, 提示调控MDS患者细胞凋亡和恶性克隆增殖可能是两种完全不同的机制。
- 骨髓增生异常综合症 /
- bcl-2 /
- VEGF /
- 原位凋亡 /
- TUNEL
Abstract: Objective This work aims to investigate the relationship between bcl-2 and VEGF antigen expression and the in situ apoptosis of hematopoietic cells in myelodysplastic syndrome(MDS), and to discuss the pathogenesis of MDS. Methods Through bone marrow biopsy, the degree of bone marrow hyperplasia, morphological abnormity of hematopoietic cells, and histopathological change, called abnormal localization of immature precursor(ALIP) in light microscopy were observed.Immunohistochemistry was used to monitor the bcl-2 and VEGF antigen expressions.The in situ apoptosis of hematopoietic cells was detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) method. Results Different degrees of hematopoietic abnormalities were found in all 13 cases.The two groups with refractory anemia(RA) and refractory anemia with excess of blasts(RAEB) had no significant differences.ALIP was detected in 6 cases, of which 3 were RA(3/8, 37.50%) and the other 3 were RAEB(3/5, 60.00%).Positive VEGF expression was observed in 9 cases, of which 6 were RA(6/8, 750%) and the other 3 were RAEB(3/5, 60.00%).Positive bcl-2 expression was found in 7 cases, including 4 with RA(4/8, 50.00%) and three with RAEB(3/5, 60%).All patients had positive TUNEL results.The patients with ALIP showed higher degrees of in situ apoptosis of hematopoietic cells. Conclusion MDS patients have various degrees of abnormal apoptosis of hematopoietic cells.The TUNEL method is simple, practical, sensitive, convenient, and specific tool for detecting in situ cell apoptosis.However, the mechanisms in hematopoietic cell apoptosis and clonally malignant proliferation in MDS patients may differ greatly.
- Myelodysplastic syndrome(MDS) /
- bcl-2 /
- VEGF /
- in situ apoptosis /
- TUNEL

HTML全文

图 1 免疫组织化学染色检测bcl-2和VEGF(×400)

Figure 1. Immunohistochemical staining of bcl-2 and VEGF

下载: 全尺寸图片幻灯片

图 2 TUNEL法检测细胞原位凋亡(×200)

Figure 2. In situ cell apoptosis detected by TUNEL method

下载: 全尺寸图片幻灯片

表 1 13例患者临床情况及骨髓ALIP、VEGF、bcl-2、TUNEL检测结果

Table 1. Clinical situation and results of detection for ALIP, VEGF, and bcl-2 using the TUNEL method in 13 patients

参考文献(10)

[1]	Shimazaki K, Ohshima K, Suzumiya J, et al. Evaluation of apoptosis as a prognostic factor in myelodysplasdc syndromes[J]. Br J Haematol, 2000, 110(3): 584-590. doi: 10.1046/j.1365-2141.2000.02228.x
[2]	张之南, 沈悌, 主编. 血液病诊断及疗效标准[M]. 第3版. 北京: 科学出版社, 2007: 100.
[3]	Sekeres MA. The myelodysplasdc syndromes[J]. Expert Op in Biol Ther, 2007, 7(3): 369-377. doi: 10.1517/14712598.7.3.369
[4]	Parker JE, Mufti GJ, Rasool F, et al. The role of apoptosis, proliferation, and the Bel—2—related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS[J]. Blood, 2000, 96(12): 3932-3938. doi: 10.1182/blood.V96.12.3932
[5]	Michalopoulou S, Micheva I, Kouraklis—Symeonidis A, et al. Impaired clonogenic growth of myelodysplastic bone marrow progenitors in vitro is irrelevant to their apoptotic state[J]. Leuk Res, 2004, 28(8): 805-812. doi: 10.1016/j.leukres.2003.12.004
[6]	Badran A, Yoshida A, Wano Y, et al. Expression of the anti—apoptotic gene survivin in myelodysplastic syndrome[J]. Int J Oncol, 2003, 22(1): 59-64.
[7]	Invernizzi R, Travaglino E, Lunghi M, et al. Survivin expression in acute leukemias and myelodysplastic syndromes[J]. Leuk Lympho- ma, 2004, 45(11): 2229-2237. doi: 10.1080/10428190412331283251
[8]	Dias S, Shmelkov SV, Lam G, et al. VEGF(165) promotes survival of leukemic cells by HSP90-mediated induction of Bd-2 expression and apoptosis inhibition[J]. Blood, 2002, 99(22): 2532-2540.
[9]	Bellamy WT, Richter L, Sirjani D, et al. Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes[J]. Blood, 2001, 97(5): 1427-1434. doi: 10.1182/blood.V97.5.1427
[10]	孙慧, 马杰. Survivin、Bcl-2和VEGF在骨髓增生异常综合征中的表达及其相关性[J]. 中国实验血液学杂志, 2006, 14(2): 271-275. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY200602015.htm