Association of IgVH mutation status and plasma levels of angiogenic activators in chronic lymphocytic leukaemia: significantly higher bFGF but not VEGF in IgVH mutated patients

Chronic lymphocytic leukemia (CLL) is a disease with an extremely variable clinical course. New prognostic factors such as mutation status of immunoglobulin heavy chain variable region (IgVH) or genetic aberrations can identify patients with high risk disease. Several studies have shown that angiogenesis is increased in B-CLL and may potentially serve as a new prognostic factor. To assess relationship between plasma concentrations of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) and IgVH mutational status, we measured VEGF and bFGF using sandwich enzyme-linked immunosorbent assay (ELISA) kits in peripheral blood plasma of 49 patients with untreated B-CLL and 50 healthy donors. IgVH mutation status was determined in all B-CLL patients. Mutated IgVH genes (i. e. more than 2 % difference from corresponding germline) were present in 26 and unmutated in 23 patients. There was statistically significant increase of both VEGF (p = 0.006) and bFGF (p < 0.0001) in patients with B-CLL compared to the control group. Patients with mutated IgVH genes had significantly higher concentrations of bFGF (p = 0.015) but not VEGF (p = 0.078) than those with unmutated IgVH. Conclusions: In our study, crucial angiogenic activators VEGF and bFGF were significantly elevated in peripheral blood plasma over controls. In addition, bFGF was significantly elevated in IgVH mutated vs. unmutated patients. Our findings underline the importance of bFGF signalling in B-CLL and clearly warrant further ivestigations in a larger patient cohort with longer follow-up in order to confirm the results and to determine the prognostic significance of angiogenic factors on B-CLL patients‘ clinical outcome.
Supported by grant IGA NR/8373-3 from Ministry of Health of Czech Republic.