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High Levels of Vascular Endothelial Growth Factor Receptor-2 Correlate with Shortened Survival in Chronic Lymphocytic Leukemia

Departments of Leukemia [A. F., M. J. K., S. O’B., S. L., M. B., H. M. K., E. J. F.], Hematopathology [T. M., M. A.], and Bioimmunotherapy [Z. E.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Vascular endothelial growth factor receptor-2 (VEGFR-2), also termed KDR, is a high-affinity vascular endothelial growth factor (VEGF) receptor. VEGFR-2 plays a role in de novo blood vessel formation and hematopoietic cell development. 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 VEGFR-2 is present in peripheral blood CLL cells. We then quantified the cellular levels of VEGFR-2 protein using a solid-phase radioimmunoanalysis in peripheral blood cells from 216 patients with CLL. As control, we used peripheral blood mononuclear cells (PBMNCs) from 31 hematologically normal individuals. The median of VEGFR-2 levels detected in the control samples was assigned a value of 1.0, and VEGFR-2 protein levels were normalized to the control median value. The median level of VEGFR-2 in CLL cells was 1.57. Patients with VEGFR-2 levels higher than 1.57 had elevated lymphocyte counts, severe anemia, elevated ß₂-microglobulin and advanced-stage disease. Elevated VEGFR-2 levels were also associated with statistically significantly shorter survival (35.4 versus 60.1 months; P < 0.01). Our data indicate that cellular VEGFR-2 levels may serve as a prognostic factor in CLL. Further studies should investigate the biological implications of these findings and the effect of the interaction between VEGF and VEGFR-2 on CLL cell proliferation.

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