Abstract
Angiogenesis is a process of blood vessel formation from the preexisting capillaries. It plays an essential role of growth and development of cancer. The aim of this study was to evaluate serum levels of the most important angiogenic stimulators, Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) in children with acute lymphoblastic leukemia (ALL) and their relation to clinical manifestations of the disease, and in healthy controls. Although VEGF and bFGF have been suggested to be reliable prognostic indicators and important tools for treatment approach in hematopoietic malignancies and solid tumors, experience in childhood ALL has been limited. Patients and methods: 46 children with ALL (24 male, 22 female) aged 2-18 years (median 8 years) at the time of diagnosis and in remission and 70 healthy children (31 male, 39 female). For the quantitative determination of human VEGF and bFGF, the Quantikine (R&D Systems, Minneapolis, MN, USA), a solid phase enzyme-linked immunosorbent assay method was used. Elevated VEGF and bFGF were defined as being higher than the 95 percentile value in control group. Results: The range of VEGF serum levels in healthy controls was 24.73–467.7 pg/ml (median 168.9 pg/ml), 95 percentile was 431.85 pg/ml and the range of bFGF serum levels was 0–10.8 pg/ml (median 2.9 pg/ml), 95 percentile was 6.95 pg/ml. In children with ALL, the range of VEGF serum levels at the time of diagnosis was 0–532.3 pg/ml (median 91.18 pg/ml), and bFGF 0–64.48 pg/ml (median 5.11 pg/ml). In children in remission, the range of serum levels of VEGF was 53.15–962.67 pg/ml (median 209.73 pg/ml), and bFGF 0–32.5 pg/ml (median 5.98 pg/ml). The median level of VEGF at diagnosis was lower than those of the control group (p=0.006), and higher in remission, when compared to values obtained in children on diagnosis and in the control group (p=0.0005; p=0.01). Elevated level of VEGF was observed in 8.7% children at the time of diagnosis and in 24.4% of patients in remission. The median levels of bFGF at diagnosis and in remission were significantly higher than those in control group with 40% of children having elevated levels. A positive correlation between VEGF serum concentration and platelet number, and negative correlation between VEGF serum levels and WBC were observed, with no other correlations between growth factors (VEGF, bFGF) and age, type of lymphoblasts (FAB), risk group, and drug resistance. Conclusion: These results suggest that bFGF more than VEGF can play an important role in childhood ALL. The serum levels of angiogenic factors may be related to the activity of the disease, while both growth factors can possibly be a target of anti-angiogenic therapy.
Assessment of angiogenesis in children with acute lymphoblastic leukemia based on serum vascular endothelial growth factor assay
