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SDF-1/CXCR4在骨髓增生异常综合征患者中的生物学作用
作者姓名:Yang R  Pu J  Guo J  Xu F  Zhang Z  Zhao YS  Zhang X  Gu SC  Chang CK  Li X
作者单位:1. 上海市交通大学附属第六人民医院血液科,上海200233;苏州大学医学部,江苏苏州215123
2. 桂林医学院附属医院血液科,广西桂林,541001
3. 上海市交通大学附属第六人民医院血液科,上海,200233
摘    要:本研究主要探讨骨髓增生异常综合征(MDS)及白血病患者中基质细胞衍生因子-1(SDF-1)在细胞凋亡、迁移和黏附中的作用及相关的信号转导。选取37例初发MDS患者〔低危组(IPSS≤1.0)22例,高危组(IPSS≥1.5)15例〕、10例初发白血病患者及14例良性贫血患者(作为对照组),通过流式细胞术检测骨髓CD34+细胞表面CXCR4的表达水平及CD34+细胞的凋亡情况。选取4例低危MDS患者和5例高危MDS患者,通过微孔细胞迁移实验检测SDF-1对细胞的趋化作用。通过CCK-8法检测SDF-1对细胞之间黏附能力的影响。结果表明,低危MDS组骨髓内CD34+细胞的凋亡率明显高于高危MDS组(21.33%vs 7.27%,p<0.001),同样低危MDS组骨髓内CD34+细胞的凋亡率明显高于白血病组(21.33%vs 7.53%,p<0.001),未发现CD34+细胞的凋亡率与患者年龄性别有相关性。SDF-1能够促进高表达CXCR4患者的细胞黏附于基质细胞并能诱导该细胞的迁移,诱导细胞形态发生极化,上述作用可以被G蛋白抑制剂pertussis toxin、PI3K抑制剂wortmannin及CXCR4拮抗剂AMD3100明显抑制;而对低表达CXCR4的患者细胞则无上述抑制作用。结论:SDF-1/CXCR4通过PI3K信号通路提高细胞的迁移及黏附能力,发挥抗凋亡作用,上述作用可以被PI3K途径抑制剂和G蛋白抑制剂所阻断。

关 键 词:SDF-1/CXCR4  骨髓增生异常综合征  AMD3100  pertussis  toxin  wortmannin

Biological behavior of SDF-1/CXCR4 in patients with myelodysplastic syndrome
Yang R,Pu J,Guo J,Xu F,Zhang Z,Zhao YS,Zhang X,Gu SC,Chang CK,Li X.Biological behavior of SDF-1/CXCR4 in patients with myelodysplastic syndrome[J].Journal of Experimental Hematology,2011,19(6):1432-1437.
Authors:Yang Rui  Pu Jie  Guo Juan  Xu Feng  Zhang Zheng  Zhao You-Shan  Zhang Xi  Gu Shu-Cheng  Chang Chun-Kang  Li Xiao
Institution:YANG Rui1,2,PU Jie3,GUO Juan1,XU Feng1,ZHANG Zheng1,ZHAO You-Shan1,ZHANG Xi1,GU Shu-Cheng1,CHANG Chun-Kang1,LI Xiao1 1Department of Hematology,Shanghai Sixth People Hospital,Shanghai Jiaotong University,Shanghai 200233,China,2Suzhou University Health Science Center,Suzhou 215123,Jiangsu Province,3Department of Hematology,Guilin Medical College Affiliated Hospital,Guilin 541000,Guangxi Province
Abstract:The purpose of this study was to evaluate the biological behavior of stromal cell-derived factor-l(SDF-1) in migration,adhesion and apoptosis as well as the related signaling transduction pathways in patients with myelodysplastic syndrome(MDS) and acute myeloid leukemia(AML).37 patients with MDS,10 patients with de novo AML and 14 patients with non-clonal cytopenia diseases were chosen for this study. The expression level of CXCR4 on CD34+ cells and apoptosis of CD34+ cells in bone marrow were detected by f...
Keywords:SDF-1/CXCR4  myelodysplastic syndrome  AMD3100  pertussis toxin  wortmannin  
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