High levels of vascular endothelial growth factor receptor-2 correlate with shortened survival in chronic lymphocytic leukemia

Vascular endothelial growth factor receptor-2 (VEGFR-2), also termed KDR, i s a high-affinity vascular endothelial growth factor (VEGF) receptor. VEGFR -2 plays a role in de novo blood vessel formation and hematopoietic cell de velopment. Recently, we found that chronic lymphocytic leukemia (CLL) cells express high levels of VEGF, Therefore, we sought to investigate the role of VEGFR-2 in CLL. Using Western blot analysis, we first determined that VE GFR-2 is present in peripheral blood CLL cells. We then quantified the cell ular levels of VEGFR-2 protein using a solid-phase radioimmunoanalysis in p eripheral blood cells from 216 patients with CLL, As control, we used perip heral blood mononuclear cells (PBMNCs) from 31 hematologically normal indiv iduals, The median of VEGFR-2 levels detected in the control samples was as signed a value of 1.0, and VEGFR-2 protein levels were normalized to the co ntrol median value. The median level of VEGFR-2 in CLL cells was 1.57. Pati ents with VEGFR-2 levels higher than 1.57 had elevated lymphocyte counts, s evere anemia, elevated beta (2)-microglobulin and advanced-stage disease. E levated VEGFR-2 levels were also associated with statistically significantl y shorter survival (35.4 versus 60.1 months; P < 0.01). Our data indicate t hat cellular VEGFR-2 levels may serve as a prognostic factor in CLL, Furthe r studies should investigate the biological implications of these findings and the effect of the interaction between VEGF and VEGFR-2 on CLL cell prol iferation.