Choice of endothelial marker is crucial for assessment of bone marrow microvessel density in chronic lymphocytic leukemia

Abstract

Angiogenesis is a potential prognostic factor in chronic lymphocytic leukemia (CLL). Elevated circulating levels of angiogenic factors in CLL have been repeatedly reported. Nevertheless, the issue of bone marrow neovascularization in CLL remains controversial, partly due to limited number of published studies, different methods of assessing microvessel density (MVD) and small patient cohorts. Moreover, there are very scarce data regarding the relationship of marrow angiogenesis to prognostic markers in CLL. Our objectives were: 1. To assess bone marrow MVD in CLL using two different monoclonal antibodies and a reproducible method of MVD quantification; 2. To examine the possible association of marrow MVD and clinical course, pattern of marrow infiltration, Rai stage, cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH), and mutation status of immunoglobulin heavy chain variable region (IgVH). MVD was higher using CD34 vs vWF antibody (p<0.0001). However, no MVD differences were detected between CLL subgroups subdivided according to the above-mentioned prognostic factors. In conclusion, MVD assessment using anti-CD34 resulted in higher MVD counts than when using anti-vWF antibody. No association of MVD with any prognostic factors was observed, possibly due to the limited patient cohort. As the need for bone marrow trephine biopsies in CLL is significantly decreasing, a standardized method of neovascularization assessment is required to enable possible multicentre studies in order to conduct larger investigations and thereby shed more light on the real clinical significance of bone marrow angiogenesis in CLL.