Circulating CD34+, CD133+, and vascular endothelial growth factor receptor 2-positive endothelial progenitor cells in myelofibrosis with myeloid metaplasia.
OBJECTIVE
Endothelial progenitor cells (EPCs) are present in circulation and contribute to vasculogenesis in adults. We measured the number of circulating EPCs in patients with myelofibrosis with myeloid metaplasia (MMM), and we examined the relationship between the number of EPCs and severity of the MMM disease process.


METHODS
The number of EPCs was measured by assaying the CD34+CD133+ vascular endothelial growth factor receptor 2 (VEGFR2) -positive cell phenotype in 110 MMM patients, 16 patients with other Philadelphia-negative chronic myeloproliferative disorders (Ph-negative CMPDs), and 14 healthy participants. In four MMM patients, the capacity of selected CD34+ cells to form endothelial colonies (CFU-End) in vitro was tested.


RESULTS
CD34+, CD133+, and VEGFR2-positive EPCs were detectable in unselected peripheral-blood cells of 50.9% MMM patients, 37.5% control patients, and 21% healthy participants. Patients with MMM had a median of 0.26% EPCs, significantly higher than that in healthy controls (median, 0%) and in patients with other Ph-negative CMPDs (median, 0.1%). In 14.5% of MMM patients, the numbers of EPCs were greater than the highest value found in patients with other Ph-negative CMPDs. CD34+ selected cells produced colony-forming unit-endothelial (CFU-End), which were vascular endothelial (VE) -cadherin positive, CD31+, von Willebrand factor positive, and CD45-. In MMM patients, the larger the number of EPCs, the smaller the number of circulating immature myeloid cells and circulating CD45+CD34+ hematopoietic progenitor cells. Increased numbers of EPCs were associated with younger age and a diagnosis of prefibrotic MMM.


CONCLUSIONS
Circulating EPCs are elevated in MMM patients in the early stage of the disease. Heightened mobilization of EPCs may represent an important mechanism for development of neoangiogenesis in MMM.
Massa
Margherita
M
Laboratory of Biotechnology, Italy.
Rosti
Vittorio
V
Ramajoli
Isabella
I
Campanelli
Rita
R
Pecci
Alessandro
A
Viarengo
Gianluca
G
Meli
Valentina
V
Marchetti
Monia
M
Hoffman
Ronald
R
Barosi
Giovanni
G
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000097:blood*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood*; D055728:Primary Myelofibrosis / Q000097:blood*; D018709:Statistics, Nonparametric; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D040301:Vascular Endothelial Growth Factor Receptor-2