He Qi-Tu, Bai Xue-Qin, Liu Xue-Wen, Xu Ning, Lu Yan, Zhang Dong-Xia, Li Jing, Yun Yan, Li Zhi-Qin, Han Hai-Yan, Han Xuan-Mao, Ma Hong-Jie, Zhao Zhi-Ying, Jia Guo-Rong, Li Zhe, Yuan Xiao-Jun
Department of Hematology, The First Affiliated Hospital of Baotou Medical College,Baotou 014010, Inner Mongolian Autonomous Region, China. E-mail:
Department of Hematology, The First Affiliated Hospital of Baotou Medical College,Baotou 014010, Inner Mongolian Autonomous Region, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Jun;22(3):653-9. doi: 10.7534/j.issn.1009-2137.2014.03.015.
This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively. The results showed that the mRNA and protein expression levels of above mentioned 4 factors were significantly higher than those in control (P < 0.05), only CTGF mRNA expression in AL patients after complete remission showed statistical difference as compared with control (P < 0.05), but the expression of CTGF mRNA showed statistical significance in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF protein showed difference in different chromosome karyotypes of leukemia (P < 0.05). The expression levels of CYR61 and VEGF-C proteins showed statistical difference in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF, CYR61, VEGF-C mRNA and protein in CML group were higher than that in control group. The expression levels of CTGF and CYR61 protein were higher than that in control. The mRNA and protein expression levels of above-mentioned 4 factors in sex and infiltration lf leukemic cells did not show statistical significance(P < 0.05). In correlative analysis, the mRNA expressions of above mentioned 4 factors were positively correlated with bone marrow blast count(P < 0.05), the protein expression of CTGF, CYR61 and VEGF-C were positively correlated with bone marrow blast count. It is concluded that the CTGF, CYR61, VEGF-C and VEGFR-2 mRNA and protein play a role in acute leukemia. In acute leukemia (AML/ALL), the expression of above mentioned factor was high, but except VEGFR-2. Most of them were positively correlated with bone marrow blast count. Joint block of these angiogenesis-related factors is likely to play an important role in targeting treatment of leukemia.
本研究旨在探讨白血病患者骨髓中结缔组织生长因子（CTGF）、富含半胱氨酸的血管生成素61（CYR61）、血管内皮生长因子C（VEGF-C）及血管内皮生长因子受体2（VEGFR-2）的mRNA及蛋白表达情况，分析这4种因子在白血病发生发展、白血病细胞浸润及转移中的作用及临床意义。本研究共纳入100例新诊断白血病患者、26例急性白血病完全缓解患者及30例对照者。采集骨髓单个核细胞，分别采用实时荧光定量PCR及蛋白质印迹法检测白血病患者及对照者骨髓中CTGF、CYR61、VEGF-C、VEGFR-2的mRNA及蛋白表达水平。结果显示，上述4种因子的mRNA及蛋白表达水平均显著高于对照组（P<0.05）；仅急性白血病患者完全缓解后CTGF mRNA表达与对照组相比有统计学差异（P<0.05），但CTGF mRNA表达在急性白血病不同骨髓增生程度中有统计学意义（P<0.05）；CTGF蛋白表达在白血病不同染色体核型中有差异（P<0.05）；CYR61及VEGF-C蛋白表达在急性白血病不同骨髓增生程度中有统计学差异（P<0.05）；慢性髓系白血病（CML）组CTGF、CYR61、VEGF-C的mRNA及蛋白表达水平均高于对照组；CTGF及CYR61蛋白表达高于对照组；上述4种因子的mRNA及蛋白表达在性别及白血病细胞浸润方面无统计学意义（P<0.05）。相关性分析显示，上述4种因子的mRNA表达均与骨髓原始细胞计数呈正相关（P<0.05），CTGF、CYR61及VEGF-C蛋白表达与骨髓原始细胞计数呈正相关。结论：CTGF、CYR61、VEGF-C及VEGFR-2的mRNA及蛋白在急性白血病中发挥作用。在急性白血病（AML/ALL）中，上述因子表达均高，但VEGFR-2除外。多数因子与骨髓原始细胞计数呈正相关。联合阻断这些血管生成相关因子可能在白血病靶向治疗中发挥重要作用。
