VEGF和MDR1在急性髓系白血病中的表达及其与预后关系研究

Expression of VEGF and MDR1 in acute myeloid leukemia patients and the relation with prognosis

目的研究初治急性髓系白血病(AML)患者化疗前后血清VEGF的表达及骨髓白血病细胞MDR1的表达。探讨VEGF与MDR1的表达对AML预后中的评价作用。方法血清VEGF的含量采用双抗体夹心酶联免疫吸附法检测,MDR1的表达采用直接免疫荧光标记单抗流式细胞仪(FCM)检测。结果初发和未缓解AML患者血清VEGF水平明显高于正常对照组和AML完全缓解(CR)组(P<0.01);未缓解患者血清VEGF含量与CR组比较差异有显著性意义(P<0.01),而与初治组比较差异无显著性意义(P>0.05)。初发AML患者骨髓单个核细胞的P-gp表达为(9.20±3.13)%。初发和未缓解AML患者骨髓白血病细胞的P-gp表达高于正常对照组和AML缓解组(P<0.01);P-gp表达与VEGF表达具有一定的相关性(r=0.639,P<0.01)。结论AML患者血清VEGF水平一定程度上可能反映体内白血病细胞的总负荷量同时与临床病情变化密切相关,可作为判断预后的指标之一。AML患者P-gp阳性表达者疗效差、预后不良。AML患者VEGF与P-gp的表达呈正相关,同时检测这两项指标对于AML的预后判断较单独检测更有意义。

Objective To investigate the expression of VEGF and MDRI in newly - diagnosed untreated patients with acute myeloid leukemia（AML） and to explore their correlation with prognosis. Methods VEGF in serum was measured with enzyme - linked immunosorbent assay （ ELISA ） and P - gp in bone marrow leukemic cell was analyzed by flow cytometry using FITC conjugated monoclonal antibody. Results The serum VEGF concentrations in the patients with newly - diagnosed untreated and NR group were significantly higher than the levels of the control and CR groups（ P 〈0.01 ）. The serum levels of VEGF in NR group were higher than that of the newly - diagnosed patients, but had no significant difference （P 〉0.05）. The expression level of P -gp in newly -diagnosed AML patients was significantly higher than those of the control and the CR groups（ P 〈0. 01）. Significant correlation was observed between P - gp and VEGF in newly diagnosed AML cases （ r = 0. 639 ,P 〈0. 01）. Higher level of VEGF was always accompanied by P - gp positive ,which led to a worse outcome. The patients with lower level of VEGF and P - gp negative had a higher CR rate. Conclusion The pretherapeutic serum VEGF level of AML case reflects the tumor borden of AML, and appears to be an effective predictor with the clinical features, disease condition, chemotherapy outcome and prognosis. Expression of MDR1 could be identified as an independent adverse prognostic factor for CR and survival in patients with AML. There is a linear correlation between VEGF concentration and P - gp expression in AML. Test of the two targets together is more effective to the judgement of prognosis in AML.