Circulating vascular endothelial growth factor (VEGF) and its soluble receptors in patients with chronic lymphocytic leukemia

The vascular endothelial growth factor (VEGF) transduction pathway may be very active in B-cell chronic lymphocytic leukemia (B-CLL) cells and contributes to their enhanced survival. Vascular endothelial growth factor receptor-1 (VEGFR-1) and receptor-2 (VEGFR-2), are the high-affinity VEGF receptors, which play an important role in de novo blood vessel formation and hematopoietic cell development. The aim of our study was to compare the concentration of VEGF, VEGFR-1 and VEGFR-2 in the serum of 83, never-treated B-CLL patients in different stage of disease according to Rai classification, and 20 healthy volunteers. Of all the cytokines only the serum concentration of VEGF was found to be significantly higher in the CLL group when compared to the control group (median 468.2 pg/mL and 246.9 pg/mL, respectively) (p = 0.01). In the group of CLL patients, the serum concentrations of VEGF and VEGFR-2 were significantly higher in patients in Rai stage III and IV (median 890.0 pg/mL and 4680.4 pg/mL respectively) than in patients in Rai stage 0-II (347.8 pg/mL and 2411.6 pg/mL respectively) (p<0.0001). In the entire group of CLL patients, we have found a strong, positive correlation between the serum level of VEGF and VEGFR-2 (p = 0.00001, R = 0.46). We have also found a positive correlation between the number of lymphocytes in the peripheral blood of CLL patients and the level of VEGF (p = 0.05, R = 0.24) and VEGFR2 (p = 0.02, R = 0.29). In conclusion: VEGF and VEGF R2, but not VEGF R1, may have an important influence on the course of B-CLL.