title: Circulating endothelial cells in patients with chronic lymphocytic leukemia.
abstract: Angiogenesis is increased in B-cell chronic lymphocytic leukemia (B-CLL). We wanted to quantify and characterize the circulating endothelial cells (CECs) in patients with B-CLL and correlate with plasma angiogenesis-related factors. Using a four-color flow cytometry, we prospectively analyzed the CEC in the whole blood of 20 healthy controls and 20 patients with B-CLL. We quantified (CD45-/CD31+/CD146+) and characterized the CECs according to whether they were apoptotic (annexin stain) or activated (CD106+). We also measured plasma levels of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and thrombospondin-1 (TSP-1). Most patients (90%) had Rai stages 0-2 at the time of diagnosis. As a group, B-CLL patients had higher number of CECs (median of 26.5 cells/ml) compared (P = 0.04) to healthy controls (18.5 cells/ml). However, only four (20%) patients had elevated CEC counts, defined as >/=2 SD of the control mean (>/=53 cells/ml). The proportions of apoptotic (P = 0.83) and activated (P = 0.12) CECs were similar in both groups. B-CLL patients had higher FGF-2 (P < 0.001), lower TSP-1 (P = 0.004), and similar VEGF (P = 0.27) plasma levels. The number of CECs was not associated with Rai stage, absolute lymphocyte count, or levels of angiogenesis-related factors. CECs are increased in only a small fraction of B-CLL patients in our cohort with low rates of apoptosis and activation. While no correlation was found between CECs and clinical features, more studies in a larger patient sample size and advanced disease are necessary.
authors.affiliation: Center for Cancer and Blood Disorders, Gundersen Lutheran Health System, 1900 South Avenue, Mail Stop: EB2-001, 54601 La Crosse, WI, USA. rsgo@gundluth.org
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Go
authors.forename: Dean A
authors.initials: DA
authors.lastname: Jobe
authors.forename: Krista E
authors.initials: KE
authors.lastname: Asp
authors.forename: Steven M
authors.initials: SM
authors.lastname: Callister
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Mathiason
authors.forename: Lori A
authors.initials: LA
authors.lastname: Meyer
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Bottner
authors.forename: Craig E
authors.initials: CE
authors.lastname: Cole
authors.forename: John P
authors.initials: JP
authors.lastname: Farnen
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Frisby
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D051929:CD146 Antigen; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005434:Flow Cytometry; D006801:Humans; D015448:Leukemia, B-Cell / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood*; D017493:Leukocyte Common Antigens; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011446:Prospective Studies; D019700:Thrombospondin 1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D051929:CD146 Antigen; C497902:MCAM protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019700:Thrombospondin 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017493:Leukocyte Common Antigens