Immunophenotypic, cytogenetic and functional characterization of circulating endothelial cells in myelodysplastic syndromes.
Circulating endothelial cells (CECs) are associated with neoangiogenesis in various malignant disorders. Using flow cytometry, we studied CECs in 128 patients with myelodysplastic syndrome (MDS). MDS patients had higher CEC levels than controls (P<0.001), and an inverse relationship was found between CECs and international prognostic scoring system risk (r=-0.55, P<0.001). There was a positive correlation between marrow microvessel density and CECs, low-risk patients showing the strongest association (r=0.62, P<0.001). We calculated a progenitor-to-mature CEC ratio, which was higher in MDS patients than in healthy subjects (P<0.001), the highest values were found at diagnosis. CECs assessed by flow cytometry positively correlated with the ability to produce endothelial colony-forming cells in vitro (ECFCs; r=0.57, P=0.021), which was significantly higher in MDS patients than in controls (P=0.011). Fluorescence in situ hybridization analysis showed that a variable proportion of CECs (from 40 to 84%) carried the same chromosomal aberration as the neoplastic clone, while endothelial cells isolated from in vitro assays were negative. This study suggests that CECs reflect the abnormal angiogenesis found in MDS, especially in the early stages of the disease. The increased number of functional endothelial progenitor cells in MDS strengthens the rationale for therapeutic interventions aimed at restoring a normal interaction between hematopoietic progenitors and marrow microenvironment.
Della Porta
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MG
Division of Hematology, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. matteo@haematologica.org
Malcovati
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L
Rigolin
G M
GM
Rosti
V
V
Bonetti
E
E
Travaglino
E
E
Boveri
E
E
Gallì
A
A
Boggi
S
S
Ciccone
M
M
Pramparo
T
T
Mazzini
G
G
Invernizzi
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Lazzarino
M
M
Cazzola
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M
D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000098:blood supply; D002452:Cell Count; D019070:Cell Lineage; D002869:Chromosome Aberrations; D002999:Clone Cells / Q000473:pathology; D003114:Colony-Forming Units Assay; D018450:Disease Progression; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011446:Prospective Studies