Elevated Serum Level of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Correlates with Stage of Chronic Lymphocytic Leukemia and Resistance to Treatment

Background: B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in western world with an incidence of 3,36/100,000 in European males. It is characterized by a clonal growth of long lived, slowly proliferating mature B lymphoid cells in the bone marrow (BM), peripheral blood (PB), and lymphoid tissues. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) is a pleiotropic cytokine that plays a role in hematopoiesis and apoptosis. Angiogenesis may have a role in a pathophysiology of leukemias and antiangiogenesis therapy could have an anticancer effect.

Aim: analyze the clinical significance of serum levels of angiogenic factors and how it’s correlate with clinical stage and survival in patients with B-CLL

Methods: the enzyme-linked immunosorbent assays (ELISAs) for VEGF and bFGF were performed in 78 CLL patients and 29 healthy person as a control group. The patients was divided on low-risk disease (44 patients) and high-risk disease (34 patients).

Results: VEGF and bFGF serum levels were significantly increased in patient with high-risk disease, the median serum VEGF level was 185.66 pg/ml, compared with 72.67 pg/ml in patient with a low-risk and in control, it was 48.62 pg/ml. The difference in the VEGF levels was significant for the comparison between low- and high-risk disease (p<0.001). VEGF levels correlate with high white blood cell/lymphocyte counts, short period of time to begin treatment, disease progression, lymphocyte doubling time and worse answer to chemotherapy. No significant increase was found in bFGF serum level between low- and high-risk disease (34.06 pg/ml and 35.84 pg/ml, respectevely), but between patient and control group it was differences in serum level of bFGF (34.85 pg/ml and 7.77 pg/ml, respectively) (p<0.001).

Conclusion: as we found, serum levels of bFGF and VEGF were significantly higher in the patients with B-CLL than in controls. High serum level of VEGF and bFGF associated with poor prognosis and worse answer on treatment. In summary, our data suggest that angiogenic factors play a significant role in the leukemic process and may suggest novel therapeutic approaches in B-CLL.