急性白血病患者血管内皮生长因子及其受体表达的动态观察  

Dynamic observation of vascular endothelial growth factor (VEGF)/VEGF-receptors expression in acute leukemia

作　　者：王晨[1] 陈芳源[1] 朱建善[2] 许雁萍[2] 韩洁英[1] 欧阳仁荣[1] 

机构地区：[1]上海第二医科大学附属仁济医院血液科 [2]上海第二医科大学附属仁济医院病理科,200001

出　　处：《中华内科杂志》2004年第11期845-848,共4页Chinese Journal of Internal Medicine

摘　　要：目的　探讨急性白血病 (AL)患者治疗前后骨髓中血管内皮生长因子 (VEGF)及其受体的表达差异以及这种表达与血管生成的相关性。方法　应用EnVision免疫组织化学二步法 ,检测12 2例次成人AL患者骨髓中造血细胞VEGF及其两种特异性受体fms 样酪氨酸激酶受体 (Flt 1)、激酶插入嵌合受体 (KDR)蛋白的表达情况。结果　化疗后获得完全缓解 (CR)的患者 ,其VEGF、KDR蛋白的表达在治疗前为 6 0 ( 3 3～ 12 0 )和 5 3( 3 3～ 8 0 ) ,获CR后为 5 3( 3 3～ 9 0 )和 2 0( 1 0～ 4 0 )差异有显著性 (P <0 0 5 ;P <0 0 1) ,而在化疗后未获得CR患者中的表达差异无显著性。在缓解后复发患者中的表达又升高到初发时的水平。各组初发患者Flt 1的表达水平与对照组之间差异无显著性 ,但CR期Flt 1的表达水平在CR组为 3 3( 1 7～ 5 3) ,复发组为 3 3( 2 0～ 5 3)与初发及对照组差异有显著性 (P <0 0 1)。微血管数处于高水平组的VEGF及KDR表达显著高于微血管处于低水平组者 (P <0 0 1)。骨髓原始细胞与急性髓系白血病 (AML)初发患者VEGF和KDR的表达之间成正相关 (r =0 4 2 9,0 35 9;P =0 0 0 5 ,0 0 2 ) ;与急性淋巴细胞白血病 (ALL)初发患者VEGF的表达之间成正相关 (r =0 5 2 2 ,P =0 0 3)。结论　VEGF及其两?Objective To investigate the expression of vascular endothelial growth factor (VEGF)/VEGF-receptors and its relation to bone marrow angiogenesis in acute leukemia patients before and after chemotherapy.Methods Bone marrow biopsies from 122 cases with different stages of human acute leukemia were immunostained with anti- vascular endothelial growth factor, anti- fms-like tyrosine kinase (Flt-1) and anti- kinase-domain insert containing receptor (KDR) antibodies with envision two-step immunohistochemical staining method.Results The expression of VEGF and KDR protein in remission patients was 5.3(3.3-9.0) and 2.0(1.0-4.0) being significantly lower than newly diagnosed untreated patients 6.0(3.3-12.0) and 5.3(3.3-8.0)( P <0.05,0.01). However nonsignificant decrease was shown among non-remission patients. In relapsed patients the expression of VEGF and KDR was significantly increased as compared with that in newly diagnosed patients. Flt-1 staining levels were in the same range between the newly diagnosed untreated patients and control group ( P >0.05), but significantly increased in remission or relapse patients ,being 3.3(1.7-5.3) in the remission group and 3.3(2.0-5.3) in the relapse group ( P <0.01). Expression of VEGF and KDR protein was significantly higher in patients with a high degree of bone marrow microvessel counts as compared with those with a low degree and the expression correlated well with microvessel counts ( P <0.01). There was a positive correlation of the percentage of bone marrow blasts with VEGF and KDR expression in AML patients ( r =0.429, 0.359; P =0.005, 0.02), and with VEGF expression in ALL patients ( r =0.522; P =0.03). Conclusion VEGF and its two specific cellular receptors are expressed in both haematopoietic cells and endothelial cells. VEGF may be a autocrine factor and modulates the angiogenic reaction in bone marrow as a paracrine factor. VEGF and its cellular receptor KDR may constitute promising targets for antiangiogenic and antileukemic treatment strategies

关 键 词：患者 VEGF KDR 初发 表达水平 骨髓 血管内皮生长因子 激酶 表达差异 蛋白 

分 类 号：R733.71[医药卫生—肿瘤]