PTEN、VEGF、COX-2与JAK2 V617F突变阳性骨髓增殖性肿瘤血管新生  

PTEN,VEGF,COX-2 and angiogenesis in JAK2 V617F positive myeloroliferative neoplasms

作　　者：成志勇[1] 付建珠 徐倩[1,2] 赵亚玲[1,2] 刘桂敏[1,2] 卞永生[1] 梁丽青[1] 万建设[1] 张丽军[1,2] 

机构地区：[1]保定市第一医院血液内科,河北保定071000 [2]承德医学院,河北承德067000

出　　处：《中国病理生理杂志》2016年第5期938-942,共5页Chinese Journal of Pathophysiology

基　　金：河北省重点研发计划项目(No.162777120D)

摘　　要：目的:观察PTEN、VEGF、COX-2在JAK2 V617F突变阳性骨髓增殖性肿瘤(MPN)患者骨髓中的表达与血管新生之间的相互关系。方法:收集保定市第一医院住院及门诊42例JAK2V617F阳性的MPN患者(初治组27例,治疗组15例),其中原发性血小板增多症(ET)17例,真性红细胞增多症(PV)10例,原发性骨髓纤维化(PMF)15例;此外,选取10例特发性血小板减少性紫癜(ITP)患者作为对照。Real-time PCR检测突变型与野生型JAK2比值。免疫组化检测患者及对照骨髓病理切片p-JAK2、PTEN、VEGF、COX-2的蛋白水平及CD105标记的微血管密度(MVD)。结果:初治患者p-JAK2、VEGF、COX-2及MVD水平明显高于对照组,而PTEN表达水平明显低于对照组。治疗组患者p-JAK2、VEGF、COX-2及MVD的水平明显低于初治组,但PTEN表达水平高于初治组。JAK2V617F突变量与VEGF、COX-2及MVD呈正相关(P<0.05)。PTEN与VEGF及MVD负相关(P<0.05)。JAK2突变型与野生型比值≥0.5的患者p-JAK2、VEGF、COX-2及MVD均明显高于比值<0.5的患者,而PTEN与上述相反。结论:PTEN、VEGF、COX-2与JAK2 V617F共同参与了骨髓增殖性肿瘤患者血管新生。AIM： To investigate the expression of PTEN,VEGF and COX-2,and the relationship with angiogenesis in the bone tissues of JAK2 V617 F mutation positive myeloroliferative neoplasm（ MPN） patients. METHODS：JAK2 V617 F positive MPN patients（ n = 42） were selected in the First Hospital of Baoding including 25 cases of newly diagnosed group and 17 cases of treatment group with IFN-α 2b,and 10 cases of idiopathic thrombocytopenic purpura（ ITP）patients served as controls. The ratio of mutant and wild type JAK2 was detected by real-time PCR. The protein levels of pJAK2,PTEN,VEGF and COX-2,and microvascular density（ MVD） marked with CD105 in pathological tissues of bone marrow were detected by immunohistochemistry. RESULTS： The levels of p-JAK2,VEGF,COX-2 and MVD in newly diagnosed group were significantly higher than those in control group. However,the expression level of PTEN was significantly lower than that in control group. The levels of p-JAK2,VEGF,COX-2 and MVD in treatment group were significantly lower than those in newly diagnosed group,while the expression level of PTEN was significantly higher than that in newly diagnosed group. JAK2 V617 F mutation burden was positively correlated with VEGF,COX-2 and MVD（ P〈0. 05）.PTEN was negatively correlated with VEGF and MVD（ P〈0. 05）. The levels of p-JAK2,VEGF,COX-2 and MVD in JAK2 V617 F / JAK2 ratio ≥0. 5 group were significantly higher than those in JAK2 V617 F / JAK2 ratio 0. 5 group,but PTEN showed the contrary to the above. CONCLUSION： PTEN,VEGF,COX-2 and JAK2 V617 F are involved in the pathogenesis of angiogenesis in MPN patients.

关 键 词：骨髓增殖性肿瘤 JAK2 V617F VEGF 微血管密度 血管新生 

分 类 号：R363[医药卫生—病理学]