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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。
OBJECTIVE: To observe the correlation between the expression of PTEN, VEGF and COX-2 in bone marrow of patients with JAK2 V617F mutation-positive myeloproliferative neoplasm (MPN) and angiogenesis. Methods: Totally 42 JAK2V617F positive MPN patients (27 in initial treatment group and 15 in treatment group) were enrolled in outpatient and outpatient department of Baoding First Hospital, including 17 cases of essential thrombocythemia (ET), 17 cases of polycythemia ) And 10 cases of primary myelofibrosis (PMF). In addition, 10 patients with idiopathic thrombocytopenic purpura (ITP) were selected as controls. Real-time PCR detection of mutant and wild-type JAK2 ratio. The protein levels of p-JAK2, PTEN, VEGF, COX-2 and CD105-labeled microvessel density (MVD) in patients and controls were detected by immunohistochemistry. Results: The levels of p-JAK2, VEGF, COX-2 and MVD in newly diagnosed patients were significantly higher than those in control group, while the expression of PTEN was significantly lower than that in control group. The levels of p-JAK2, VEGF, COX-2 and MVD in the treatment group were significantly lower than those in the untreated group, but the expression level of PTEN was higher than that in the untreated group. The mutation of JAK2V617F was positively correlated with VEGF, COX-2 and MVD (P <0.05). PTEN was negatively correlated with VEGF and MVD (P <0.05). Patients with a JAK2 mutant and wild-type ratio> 0.5 had significantly higher p-JAK2, VEGF, COX-2 and MVD than patients with a ratio <0.5, whereas PTEN was the same as above. CONCLUSION: PTEN, VEGF, COX-2 and JAK2 V617F are involved in angiogenesis in myeloproliferative neoplasms.