Xu Ning, He Qi-Tu, Lu Yan, Han Xuan-Mao, Ma Hong-Jie, Zhang Dong-Xia, Liu Xue-Wen, Yuan Xiao-Jun, Jia Guo-Rong, Li Jing, Li Zhe, Li Zhi-Qin, Han Hai-Yan
Department of Hematology, Baotou Medical College First Hospital, Baotou, Inner Mongolian Autonomours Region, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2011 Dec;19(6):1368-73.
The study was aimed to detect the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in bone marrow (BM) of leukemia patients and investigate the interaction of CYR61, CTGF, VEGF-C, VEGFR-2 proteins in occurrence, development, infiltration and metastasis of leukemia and its clinical significance, to find a new tumor marker for diagnosis and treatment of leukemia with some new directions. 74 patients with leukemia were enrolled in this study, 38 out of them were males and 36 were females, aged from 6 to 77 years old with the median age of 45 years old. In the control group, 7 males and 5 females, aged from 16 to 78 years old with the median age of 46. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA. The results showed that the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in BM of newly diagnosed patients with acute and chronic leukemia of each group were significantly higher as compared with the control group (p < 0.05). The levels of CYR61, CTGF mRNA in acute leukemia remission group were significantly higher than those in control group (p = 0.039, 0.025). The level of CTGF mRNA was highest in B-ALL group, and was higher than that in AML, CML, CLL, T-ALL groups (p = 0.002, 0.034, 0.002, 0.010). In AML group, mRNA expressions of CYR61 and CTGF, CYR61 and VEGF-C, CTGF and VEGFR-2 were positively correlated (r = 0.452, 0.466, 0.464; p = 0.045, 0.038, 0.039), and in CML group mRNA expression of CYR61 and VEGF-C was positively correlated (r = 0.882, p = 0.000). The expression levels of VEGF-C, VEGFR-2 mRNA in acute leukemia patients with extramedullary infiltration were higher than those in acute leukemia patients without extramedullary infiltration (p = 0.028, 0.047). VEGF-C mRNA expression and the original cell counts in AML group were positively correlated (r = 0.418, p = 0.034). It is concluded that CYR61, CTGF, VEGF-C and VEGFR-2 interact each other in the pathogenesis of leukemia, promote the development, metastasis and infiltration of leukemia; and these factors in different types of leukemia and extramedullary infiltration are different, which may become tumor markers of leukemia; and blocking VEGF-C and VEGFR-2 may block tumor growth and metastasis.
本研究旨在检测白血病患者骨髓中CYR61、CTGF、VEGF - C、VEGFR - 2 mRNA水平，探讨CYR61、CTGF、VEGF - C、VEGFR - 2蛋白在白血病发生、发展、浸润和转移中的相互作用及其临床意义，为白血病的诊断和治疗寻找新的肿瘤标志物及新方向。本研究纳入74例白血病患者，其中男性38例，女性36例，年龄6至77岁，中位年龄45岁。对照组7例男性和5例女性，年龄16至78岁，中位年龄46岁。采用半定量逆转录聚合酶链反应（RT - PCR）检测CYR61、CTGF、VEGF - C、VEGFR - 2 mRNA水平。结果显示，各型急性和慢性白血病初诊患者骨髓中CYR61、CTGF、VEGF - C、VEGFR - 2 mRNA水平均显著高于对照组（p < 0.05）。急性白血病缓解组CYR61、CTGF mRNA水平显著高于对照组（p = 0.039，0.025）。CTGF mRNA水平在B - ALL组最高，高于AML、CML、CLL、T - ALL组（p = 0.002，0.034，0.002，0.010）。在AML组，CYR61与CTGF、CYR61与VEGF - C、CTGF与VEGFR - 2的mRNA表达呈正相关（r = 0.452，0.466，0.464；p = 0.045，0.038，0.039），在CML组CYR61与VEGF - C的mRNA表达呈正相关（r = 0.882，p = 0.000）。急性白血病髓外浸润患者VEGF - C、VEGFR - 2 mRNA表达水平高于无髓外浸润患者（p = 0.028，0.047）。AML组VEGF - C mRNA表达与原始细胞计数呈正相关（r = 0.418，p = 0.034）。结论：CYR61、CTGF、VEGF - C和VEGFR - 2在白血病发病机制中相互作用，促进白血病的发展、转移和浸润；这些因子在不同类型白血病及髓外浸润情况中存在差异，可能成为白血病的肿瘤标志物；阻断VEGF - C和VEGFR - 2可能阻断肿瘤生长和转移。
