title: Circulating endothelial cells in patients with chronic lymphocytic leukemia: clinical-prognostic and biologic significance.
abstract: BACKGROUND
  In patients with cancer, circulating endothelial cells (CECs) are increased and are correlated with an aggressive disease course. However, the clinical and biologic significance of CECs in chronic lymphocytic leukemia (CLL) remains uncertain.
  
  
  METHODS
  In 170 patients with CLL, CEC levels were quantified by flow cytometry and were correlated with clinical and biologic data. In addition, CECs were characterized by immunophenotypic, fluorescence in situ hybridization (FISH), and gene expression profile analyses.
  
  
  RESULTS
  In patients with CLL, CECs were increased compared with controls. A higher level of CECs (>20/microL) identified a subset of patients with a more aggressive disease course characterized by a shorter time to first treatment both in univariate and multivariate analyses. In FISH analysis, 7 patients had a significant proportion of CECs and presented with the same cytogenetic lesion of neoplastic lymphocytes and immunophenotypic features of endothelial progenitor cells. The gene expression profile of sorted CECs revealed a molecular pattern, suggesting a derivation from CLL leukemic cells with increased cell survival and proliferation, diminished cell adhesion to extracellular matrix, and enhanced proangiogenic function compared with their normal counterparts.
  
  
  CONCLUSIONS
  The current data suggest that, in CLL, CECs may represent a biologic marker of aggressiveness and disease progression to be considered for new, targeted antiangiogenic treatments.
authors.affiliation: Hematology Section, St. Anna University Hospital, University of Ferrara, Ferrara, Italy. rglgmt@unife.it
authors.forename: Gian Matteo
authors.initials: GM
authors.lastname: Rigolin
authors.forename: Rossana
authors.initials: R
authors.lastname: Maffei
authors.forename: Lara
authors.initials: L
authors.lastname: Rizzotto
authors.forename: Maria
authors.initials: M
authors.lastname: Ciccone
authors.forename: Olga
authors.initials: O
authors.lastname: Sofritti
authors.forename: Giulia
authors.initials: G
authors.lastname: Daghia
authors.forename: Francesca
authors.initials: F
authors.lastname: Cibien
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavazzini
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
mesh_terms: D000368:Aged; D018941:Antigens, CD19 / Q000378:metabolism; D002869:Chromosome Aberrations; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D011379:Prognosis
chemical_list: D018941:Antigens, CD19