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.

Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease

“…VEGF-A/ sVEGFR-1 index was assessed in patients with pancreatic cancer and acute myeloid leukemia with regard to the severity of the disease and prognosis (Aref et al, 2005;Chang et al, 2008). This parameter could be used in practice to assess the degree of severity of PAD, which is the subject of the current research (Rość et al, 2014).…”

Vascular Endothelial Growth Factor–Mediated Decrease in Plasma Soluble Vascular Endothelial Growth Factor Receptor-2 Levels as a Surrogate Biomarker for Tumor Growth

“…www.aacrjournals.org in a variety of cancers, including breast and colorectal carcinomas (35), melanoma (20), and a number of blood cell-related malignancies (21)(22)(23)(24); however, the utility of this protein as a potential biomarker remains unclear. To further investigate the relationship between sVEGFR-2 levels and tumor burden, we examined plasma obtained from various preclinical mouse tumor models that included spontaneous and implanted tumors, as well as localized and metastatic disease.…”

“…We first reported the existence of this 160-kDa truncated protein, which could be detected in both mouse and human plasma (19). Recent clinical studies have involved investigations into its potential as a surrogate biomarker for tumor progression or survival in melanoma (20), myelodysplastic syndromes (21), as well as in various leukemias (22)(23)(24). However, no clear pattern has yet emerged to indicate the utility of monitoring circulating sVEGFR-2 in the clinical setting, how it relates to tumor growth, and the underlying mechanisms governing observed changes.…”

Computational kinetic model of VEGF trapping by soluble VEGF receptor-1: effects of transendothelial and lymphatic macromolecular transport

“…One of the few known physiological roles of sVEGFR1 is its antiangiogenic participation in the maintenance of corneal avascularity (2). In contrast, the pathological involvement of sVEGFR1 is being discovered in a growing list of VEGF-dependent disease conditions, from preeclampsia (1,25,39) to cancers (3,4,8,23) to liver cirrhosis (18), sepsis (35), and possibly peripheral arterial disease (16).…”

“…The second and third extracellular Ig-like domains of the VEGFR1 protein are generally believed to confer its ligand-binding capacity (5,12), while the fourth Ig-like domain was found responsible for receptor dimerization (5,7). Several in vitro and in vivo studies have suggested that gene delivery of solely the first three Ig-like domains of VEGFR1 (ECD [1][2][3] ) was effective in inhibiting VEGF-mediated corporal tissue vasoreactivity in rabbits (41), as well as in inhibiting human umbilical vein endothelial cell (HUVEC) proliferation and tumor angiogenesis in mice (24,42,44). This may suggest that VEGF binding through ECD [1][2][3] alone is sufficient to simulate sVEGFR1's antiangiogenic effects.…”