Assessment of Bone Marrow Microvessel Densityin Chronic Lymphocytic Leukemia

摘要

Introduction: Angiogenesis is a physiologic process of new bloodvessels formation mediated by various cytokines called pro-angiogenic and antiangiogenic factors. Enhancement of angio-genesis in chronic lymphocytic leukemia (CLL) has beenrecognized more recently. Our study assesses CD34 and vonWillebrand factor (vWf) expression and microvessel density(MVD) in the bone marrow of patients with CLL. Aims: (1) To assess bone marrow MVD in CLL using 2 differentmonoclonal antibodies, CD34 and vWf; and (2) To examine thepossible association of marrow MVD and clinical course,pattern of marrow infiltration, Rai stage, CD38 positivity, andcytogenetic abnormalities detected by fluorescence in situhybridization. Materials and Methods: Bone marrow specimens from 33patients with CLL and 10 controls were studied. A singlemicrovessel was defined as any vessel with a clear lumen. Thescreening of the slides was carried out by hotspot method. Theslides were initially screened at low power to identify the areaswith highest number of microvessel or vascularity hotspot. Thecount of microvessel in a sufficiently extended field (40 xobjective lens, 10 x ocular lens) was then performed. The meanvalue of 10 most vascularized areas at 400 x field wasconsidered as MVD for a sample. Results: There was a significant difference between MVD countsaccording to the antibody used. MVD was higher using CD34versus vWF (CD34: mean +- SD, 35.91 +- 15.7; 95% confidenceinterval of mean, 30.34-41.48 vessels/field versus vWF:8.15 +-4.65; 95% confidence interval of mean, 4.11-12.44vessels/field; P < 0.0001]. Bone marrow MVD detected byCD34 was significantly higher in patients with CD38 expressionmore than 30% (P = 0.006) and in patients with unfavorablecytogenetic abnormalities. However, no significant MVDdifferences were detected between CLL subgroups with regardto clinical course, pattern of marrow infiltration, and Rai stage.Bone marrow MVD in patients with CLL was significantlyhigher than that in contro...