title: Hematopoietic and endothelial progenitor cell trafficking in patients with myeloproliferative diseases.
abstract: OBJECTIVE
  The presence of circulating hematopoietic progenitor cells in patients with myeloproliferative diseases (MPD) has been described. However, the exact nature of such progenitor cells has not been specified until now. The aim of this work was to investigate the presence of endothelial precursor cells in the blood of patients with MPD and to assess the role of the endothelial cell lineage in the pathophysiology of this disease.
  
  
  METHODS
  Endothelial progenitor cell marker expression (CD34, prominin (CD133), kinase insert domain receptor (KDR) or vascular endothelial growth factor receptor 2 (VEGFR2), and von Willebrand factor) was assessed in the blood of 53 patients with MPD by quantitative polymerase chain reaction. Clonogenic stem cell assays were performed with progenitor cells and monocytes to assess differentiation towards the endothelial cell lineage. The patients' were divided according to whether they had essential thrombocythemia (ET, n=17), polycythemia vera (PV, n=21) or chronic idiopathic myelofibrosis (CIMF, n=15) and their data compared with data from normal controls (n=16) and patients with secondary thrombo- or erythrocytosis (n=17).
  
  
  RESULTS
  Trafficking of CD34-positive cells was increased above the physiological level in 4/17 patients with ET, 5/21 patients with PV and 13/15 patients with CIMF. A subset of patients with CIMF co-expressed the markers CD34, prominin (CD133) and KDR, suggesting the presence of endothelial precursors among the circulating progenitor cells. Clonogenic stem cell assays confirmed differentiation towards both the hematopoietic and the endothelial cell lineage in 5/10 patients with CIMF. Furthermore, the molecular markers trisomy 8 and JAK2 V617F were found in the grown endothelial cells of patients positive for trisomy 8 or JAK2 V617F in the peripheral blood, confirming the common clonal origin of both hematopoietic and endothelial cell lineages.
  
  
  CONCLUSIONS
  Endothelial precursor cells are increased in the blood of a subset of patients with CIMF, and peripheral endothelial cells bear the same molecular markers as hematopoietic cells, suggesting a primary role of pathological endothelial cells in this disease.
authors.affiliation: Hematology Department, University Hospital, CH-3010 Berne, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Oppliger Leibundgut
authors.forename: Michael Peter
authors.initials: MP
authors.lastname: Horn
authors.forename: Claudio
authors.initials: C
authors.lastname: Brunold
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pfanner-Meyer
authors.forename: Dorothee
authors.initials: D
authors.lastname: Marti
authors.forename: Hans
authors.initials: H
authors.lastname: Hirsiger
authors.forename: Andreas
authors.initials: A
authors.lastname: Tobler
authors.forename: Caroline
authors.initials: C
authors.lastname: Zwicky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood* / Q000235:genetics; D021381:Protein Transport / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D018952:Antigens, CD34