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

 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。JAK2 V617F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。

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

AIM: To investigate the expression of PTEN, VEGF and COX-2, and the relationship with angiogenesis in the bone tissues of JAK2 V617F mutation positive myeloroliferative neoplasm(MPN)patients. METHODS: JAK2 V617F 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 p-JAK2, 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 V617F 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 V617F/JAK2 ratio≥0.5 group were significantly higher than those in JAK2 V617F/JAK2 ratio<0.5 group, but PTEN showed the contrary to the above.CONCLUSION: PTEN, VEGF, COX-2 and JAK2 V617F are involved in the pathogenesis of angiogenesis in MPN patients.