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82例急性髓系白血病患者中血管内皮生长因子与基质金属蛋白酶-2、基质金属蛋白酶-9的关系

[Relationship between VEGF and MMP-2, MMP-9 in 82 patients with acute myeloid leukemia].

作者信息

Yang Lin, Dong Zuo-Ren, Wen Shu-Peng, Pan Ling, Zhang Xue-Jun, Luo Jian-Min, Xu Shi-Rong

机构信息

Department of Hematology, The Second Hospital of Heibei Medical University, Shijiazhuang 050000, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006 Feb;14(1):15-20.

Abstract

In order to investigate the relationship between VEGF and matrix metalloproteinase (MMP)-2, -9 in acute myeloid leukemia patients, and evaluate the significance of them in extramedullary leukemic invasion, the expressions of MMP-2 mRNA, MMP-9 mRNA, VEGF mRNA in bone marrow from 86 patients with acute myeloid leukemia (AML), as well as human hematopoietic cell lines were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The proteolytic activities of MMP-2 and MMP-9 in the supernatants were measured by zymography. The VEGF protein in serum of all samples was detected by ELISA. All these results were analyzed for determination of the relationship between VEGF and MMP-2, MMP-9. The results showed that there was a positive correlation between expressions of MMP-2 mRNA or MMP-9 mRNA and VEGF mRNA or protein. But no such correlation was demonstrated in the AML (CR) and normal control (NC) groups. A higher expression level of MMP-2 and MMP-9 in the VEGF positive group was found, as compared with the negative group (P < 0.05). More extramedullary infiltration occurred in VEGF positive groups than that in VEGF negative groups of AML. The expression of bcl-2 in HL-60 cells was upregulated by VEGF. It is concluded that there are significantly positive correlations between the expression of MMP-2 and MMP-9 with VEGF mRNA or protein levels in AML patients. VEGF can upregulate the expression of MMP-2, MMP-9 in HL-60 and a part of the primary leukemic cells. VEGF and MMP-2, MMP-9 may participate in the extramedullary leukemic invasion of AML patients.

摘要

为了研究急性髓系白血病患者血管内皮生长因子(VEGF)与基质金属蛋白酶(MMP)-2、-9之间的关系,并评估它们在髓外白血病浸润中的意义,采用逆转录-聚合酶链反应(RT-PCR)分析了86例急性髓系白血病(AML)患者骨髓以及人造血细胞系中MMP-2 mRNA、MMP-9 mRNA、VEGF mRNA的表达。通过酶谱法检测上清液中MMP-2和MMP-9的蛋白水解活性。采用酶联免疫吸附测定(ELISA)法检测所有样本血清中的VEGF蛋白。对所有这些结果进行分析,以确定VEGF与MMP-2、MMP-9之间的关系。结果显示,MMP-2 mRNA或MMP-9 mRNA与VEGF mRNA或蛋白的表达之间呈正相关。但在AML(完全缓解,CR)组和正常对照组(NC)中未显示出这种相关性。与阴性组相比,VEGF阳性组中MMP-2和MMP-9的表达水平更高(P<0.05)。AML的VEGF阳性组比VEGF阴性组发生更多的髓外浸润。VEGF可上调HL-60细胞中bcl-2的表达。结论:AML患者中MMP-2和MMP-9的表达与VEGF mRNA或蛋白水平之间存在显著正相关。VEGF可上调HL-60及部分原代白血病细胞中MMP-2、MMP-9的表达。VEGF和MMP-2、MMP-9可能参与了AML患者的髓外白血病浸润。

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