Aref Salah, El Sherbiny Mamdouh, Goda Tarek, Fouda Manal, Al Askalany Hassan, Abdalla Doaa
Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura, Egypt.
Hematology. 2005 Apr;10(2):131-4. doi: 10.1080/10245330500065797.
Angiogenesis is the formation of new blood vessels and is controlled by a balance between positive and negative angiogenic regulatory factors. Soluble vascular endothelial growth factor receptors 1,2 (Flt-1, KDR) are the negative counterpoint to the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulator in human angiogenesis. In the present work, we tested the differential prognostic relevance of soluble vascular endothelial growth factor (VEGF), their receptors 1 (Flt-1), 2 (KDR), and the ratio between sVEGF/sFlt-1 in 43 patients with acute myeloid leukemia (AML). sVEGF and its soluble receptors were assessed using an ELISA. Soluble VEGF, sFLT-1 and sKDR concentration levels were significantly higher in AML patients at diagnosis when compared to the levels in normal controls. sVEGF, sFlt1 and the sVEGF/sFlt1 ratio were significantly higher in non responders when compared to responders (P < 0.001 for all). However, there was no significant difference regarding sKDR levels (P > 0.05). sVEGF, the sVEGF/sFlt1 ratio but not sFlt1 and sKDR levels were significantly elevated in those who did not survive, when compared to survivors. sVEGF, sFlt1 levels were significantly correlated to WBC counts (R = 0.93, P = 0.000, R = 0.56, P = 0.000, respectively); bone marrow blast cell counts (R = 0.92, P = 0.000; R = 56, P = 0.000, respectively); peripheral blood blast cell counts (R = 0.91, P = 0.000; R = 0.52, P = 0.000, respectively); sKDR was only correlated to peripheral blood blast cell counts(R=0.37,P=0.014). Cox regression analysis results with sVEGF, sFlt1, sKDR, sVEGF/sFlt1 ratio suggest that the most important predictor for AML outcome is the sVEGF/sFlt1 ratio. In conclusion, sVEGF/sVEGF ratio is independent predictor of AML patient out come, and its significance should be assessed when considering antiangiogenic therapy.
血管生成是新血管的形成过程，受血管生成正负调节因子之间的平衡控制。可溶性血管内皮生长因子受体1、2（Flt-1、KDR）是血管内皮生长因子（VEGF）信号通路的负向对应物，VEGF信号通路被认为是人类血管生成中最重要的内皮调节因子之一。在本研究中，我们检测了43例急性髓系白血病（AML）患者中可溶性血管内皮生长因子（VEGF）、其受体1（Flt-1）、2（KDR）以及sVEGF/sFlt-1比值的不同预后相关性。使用酶联免疫吸附测定法（ELISA）评估sVEGF及其可溶性受体。与正常对照组相比，AML患者诊断时的可溶性VEGF、sFLT-1和sKDR浓度水平显著更高。与缓解者相比，未缓解者的sVEGF、sFlt1和sVEGF/sFlt1比值显著更高（所有P<0.001）。然而，sKDR水平无显著差异（P>0.05）。与存活者相比，未存活者的sVEGF、sVEGF/sFlt1比值显著升高，但sFlt1和sKDR水平无显著差异。sVEGF、sFlt1水平与白细胞计数显著相关（分别为R = 0.93，P = 0.000；R = 0.56，P = 0.000）；与骨髓原始细胞计数显著相关（分别为R = 0.92，P = 0.000；R = 0.56，P = 0.000）；与外周血原始细胞计数显著相关（分别为R = 0.91，P = 0.000；R = 0.52，P = 0.000）；sKDR仅与外周血原始细胞计数相关（R = 0.37，P = 0.014）。对sVEGF、sFlt1、sKDR、sVEGF/sFlt1比值进行Cox回归分析结果表明，AML预后的最重要预测指标是sVEGF/sFlt1比值。总之，sVEGF/sVEGF比值是AML患者预后的独立预测指标，在考虑抗血管生成治疗时应评估其意义。
