Soluble VEGF/sFLt1 ratio is an independent predictor of AML patient out come

Abstract

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.