Circulating endothelial cells in patients with chronic lymphocytic leukemia: clinical-prognostic and biologic significance.
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.
Rigolin
Gian Matteo
GM
Hematology Section, St. Anna University Hospital, University of Ferrara, Ferrara, Italy. rglgmt@unife.it
Maffei
Rossana
R
Rizzotto
Lara
L
Ciccone
Maria
M
Sofritti
Olga
O
Daghia
Giulia
G
Cibien
Francesca
F
Cavazzini
Francesco
F
Marasca
Roberto
R
Cuneo
Antonio
A
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
D018941:Antigens, CD19