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Circulating CD34⁺, CD133⁺, and Vascular Endothelial Growth Factor Receptor 2–Positive Endothelial Progenitor Cells in Myelofibrosis With Myeloid Metaplasia

From the Laboratory of Biotechnology; the Transplant Research Area; the Unit of Internal Medicine III; the Unit of Clinical Immunology, Immunohematology, and Transfusion Service; the Department of Pediatrics; the Laboratory of Clinical Epidemiology, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy; the Section of Hematology/Oncology; Department of Pathology, University of Illinois Cancer Center; University of Illinois College of Medicine; and the Myeloproliferative Disorders Research Consortium, Chicago, IL

Address reprint requests to Giovanni Barosi, MD, Laboratorio di Epidemiologia Clinica, IRCCS Policlinico S. Matteo, Viale Golgi 19, 27100 Pavia, Italy; e-mail: barosig{at}smatteo.pv.it

PURPOSE: 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.

PATIENTS AND 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.

CONCLUSION: 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.

Supported by grant No. CS30 (2003) from Istituto Superiore di Sanità and by a grant (Ricerca Finalizzata 2002) from the Italian Ministry of Health.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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