急性髓系白血病患者造血微环境中EPCs数量、微血管密度与VEGFR-2表达的意义

Significance of EPCs Number,MVD and VEGFR-2 Expression in Hematopoietic Microenvironment of 30 Patients with Acute Myeloid Leukemia

目的探讨急性髓系白血病(AML)患者外周血及骨髓中内皮祖细胞(EPCs)的数量变化以及骨髓活检标本中微血管密度(MVD)和血管内皮生长因子受体-2(VEGFR-2)表达的临床意义。方法采用流式细胞仪检测30例AML患者以及10例健康对照组外周血及骨髓中EPCs的数量,进行相对及绝对计数;应用常规石蜡包埋骨髓病理切片进行免疫组织化学染色检测30例AML患者骨髓活组织中MVD和VEGFR-2表达水平,分析其与临床特征的关系。结果 (1)治疗前AML患者外周血和骨髓中EPCs计数与对照组比较,差异有统计学意义(P<0.01);治疗后AML患者完全缓解(CR)组与未缓解(NR)组外周血中EPCs比较,差异有统计学意义(P<0.01);CR与NR组骨髓中EPCs计数比较差异也有统计学意义(P<0.05)。(2)AML骨髓切片上MVD和VEGFR-2表达水平与健康对照组比较差异有统计学意义(P<0.05)。经Spearman秩相关检验,EPCs绝对计数、MVD、VEGFR-2三者之间呈正相关关系。(3)观察外周血中EPCs绝对计数≥20个/微升以及<20个/微升两组生存曲线,以100周为观察终点,<20个/微升组生存期明显优于前者。(4)经Cox回归分析,发现治疗前外周血EPCs绝对计数、WBC计数、VEGFR-2、β2-微球蛋白为危险因素。骨髓巨核细胞数与ECOG评分为保护因素。结论 EPCs计数结合MVD和VEGFR-2检测对评价AML血管内皮功能可能有一定的临床意义,可作为判断患者疗效及预后的指标之一。

Objective To investigate the clinical significance of MVD, change in EPCs number in peripheral blood and bone marrow, and the expression of VEGFR-2 in bone marrow biopsy specimens of patients with acute myeloid leukemia （AML）. Methods The number of EPCs was determined by FCM method in 30 patients with AML and 10 healthy cases in control group. Bone marrow pathological sections of 30 AML patients were embedded by conventional paraffin. Microvessel density（MVD） and the expression of vascular endothelial growth factor receptor-2（VEGFR-2） were detected by immunohistochemistry assay and its relationship with clinical features was analyzed. Results （1）The number of EPCs in the peripheral blood （ PB ） and bone marrow （ BM ） of patients with AML before treatment was significantly higher than that in control group（ P〈0.01 ）. After treatment, the number of EPCs of AML patients in CR group was significantly lower than that in NR group[P〈0.01（PB）; P〈0.05（BM）].（2） MVD and VEGFR-2 expression were significantly higher than that in control group（P〈0.05）. Tested by spearman rank correlations, the absolute numbers of EPCs in PB and BM had positive correlation with MVD and VEGFR-2 [P〈0.01（PB）; P〈0.05（BM）]. （3） The survival curves for 100 weeks had significant difference between groups of 〉20/gl and 〈20/gl of EPCs. （4） By Cox regression, there were risk factors including the absolute number of EPCs before treatment, the percentage of WBC, VEGFR-2 and ~2-MG. Megakaryocytic cells and ECOG performance status were protective factors. Conclusion Dynamic observation of EPCs count combined with MVD and VEGFR-2 may be clinically correlated with the evaluation of AML vascular endothelial function in a certain degree. It may be used to evaluate the treatment outcomes and act as a prognostic marker for AML.