Soluble vascular endothelial growth factor receptor 1, and not receptor 2, is an independent prognostic factor in acute myeloid leukemia and myelodysplastic syndromes

Abstract

BACKGROUND Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) are major regulators of angiogenesis, which plays a key role in the growth and dissemination of solid tumors and hematologic neoplasms. METHODS The authors measured the plasma concentrations of soluble VEGFR1 (sVEGFR1) and sVEGFR2 in 133 patients with acute myeloid leukemia (AML) and in 80 patients with myelodysplastic syndromes (MDS) at the time of initial presentation and compared clinical behaviors. RESULTS A reverse correlation was observed between plasma sVEGFR1 levels and the rate of complete remission (CR) in patients with AML, but not in patients with MDS. In contrast, increased plasma levels of sVEGFR2 were correlated with a lower CR rate in patients with MDS, but not in patients with AML. Cox regression model analysis demonstrated that plasma levels of sVEGFR1, but not sVEGFR2, were independent prognostic factors in both patients with AML and patients with MDS. CONCLUSIONS The findings suggest that different mechanisms are involved in the pathophysiology of AML and MDS. The concentration of sVEGFR1 and sVEGFR2 in plasma should be considered a significant factor in guiding antiangiogenic therapy for AML and MDS. They may play a role in the pharmacodynamics of therapeutic agents that are supposed to bind directly to these receptors. Cancer 2004. © 2004 American Cancer Society.

Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6

“…In particular, sVegFr-1 has been studied, not only as a potential surrogate marker for disease progression, but also as a potential inhibitor of tumor angiogenesis in various types of cancers (5,31). Previous studies have shown that sVEGFR-1 and/or sVegFr-2 levels in plasma were higher in cancer patients than in healthy volunteers (21,32,33). our present data also demonstrated that plasma sVegFr-1 and sVegFr-2 levels of advanced CRC patients are significantly higher than those of healthy volunteers.…”

“…Hu et al also reported that plasma sVegFr-1, but not sVegFr-2, was an independent prognostic factor in AMl and myelodysplastic syndromes (21). little is currently known regarding the potential of plasma sVegFr-1 and sVegFr-2 levels as a predictive biomarker for treatment response and survival in crc patients treated with bevacizumab-based therapy.…”

“…In addition to these receptors, circulating soluble forms of VegFr-1 (sVegFr-1) and VegFr-2 (sVegFr-2) have attracted attention as potential biomarkers of various malignancies. the sVegFr-1 has been examined both as a potential surrogate marker for disease progression and/or as a potential inhibitor of tumor angiogenesis in colon, breast and renal cell carcinoma (16)(17)(18)(19)(20)(21). However, the clinical significance of plasma sVegFr-1 and sVegFr-2 levels as biomarkers of anti-angiogenic therapy combined with chemotherapy have yet to be sufficiently investigated.…”

Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

“…A recent study of the relationship between circulating sVEGFR-1 levels and preeclampsia reported that increased sVEGFR-1 is significantly associated with the development of preeclampsia, suggesting that immunodetectable sVEGFR-1 is biologically active (Levine et al, 2004). Regarding malignancies such as brain tumours or leukaemia, it was also documented that intratumoral or plasma sVEGFR-1 level is related to tumour phenotype or prognosis, suggesting that sVEGFR-1 plays a significant biological role not only during development or pregnancy but also in neoplasms (Lamszus et al, 2003;Hu et al, 2004).…”

Elevated Levels of Plasma Angiogenic Factors Are Associated with Human Lymphatic Filarial Infections

“…Recent clinical studies have investigated the potential of sVEGFR2 as a surrogate for tumor progression in melanoma, 25 myelodysplastic syndromes, or in various leukemias. 26 Although there is no information related to the utility of monitoring sVEGFR-2 levels in filarial infections, the inverse relationship between sVEGFR-2 and VEGF-A or VEGF-C is similar to that seen in other conditions. [27][28][29] Similarly, increased levels of VEGF and reduced levels of sVEGFR-2 have been shown with the use of inhibitors of cellular VEGF receptor tyrosine kinases VEGF RTKs, including sunitinib, 30 axitinib, 31 and telatinib, 32 suggesting a receptor downregulation-mediated increase in sVEGFR-2.…”