title: Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells.
abstract: BACKGROUND
  Vascular endothelial cells lost from the blood-vessel endothelium through necrosis or apoptosis must be replaced. We investigated in a leukaemia model whether bone-marrow-derived endothelial cells contribute to this maintenance angiogenesis.
  
  
  METHODS
  We studied six patients with chronic myelogenous leukaemia (CML) carrying the BCR/ABL fusion gene in their bone-marrow-derived cells. We screened endothelial cells generated in vitro from bone-marrow-derived progenitor cells and vascular endothelium in myocardial tissue for the BCR/ABL fusion gene by in-situ hybridisation. For detection of donor-type endothelial cells after transplantation of haemopoietic stem cells, recipient tissue was stained with monoclonal antibodies against donor-type HLA antigens.
  
  
  RESULTS
  We identified the BCR/ABL fusion gene in variable proportions (0-56%) of endothelial cells generated in vitro. Endothelial cells expressing the fusion gene were found in the vascular endothelium of a patient. In a recipient of an allogeneic stem-cell transplant, normal donor-type endothelial cells were detected in the vascular endothelium.
  
  
  CONCLUSIONS
  These findings suggest that CML is not solely a haematological disease but originates from a bone-marrow-derived haemangioblastic precursor cell that can give rise to both blood cells and endothelial cells. Moreover, normal bone-marrow-derived endothelial cells can contribute to the maintenance of the blood vascular endothelium. The integration of bone-marrow-derived endothelial cells into the vascular endothelium provides a rationale for developing vascular targeting strategies in vasculopathies, inflammatory diseases, and cancer.
authors.affiliation: Division of Haematology and Oncology, University of Innsbruck, Austria. eberhard.gunsilius@uibk.ac.at
authors.forename: E
authors.initials: E
authors.lastname: Gunsilius
authors.forename: H C
authors.initials: HC
authors.lastname: Duba
authors.forename: A L
authors.initials: AL
authors.lastname: Petzer
authors.forename: C M
authors.initials: CM
authors.lastname: Kähler
authors.forename: K
authors.initials: K
authors.lastname: Grünewald
authors.forename: G
authors.initials: G
authors.lastname: Stockhammer
authors.forename: C
authors.initials: C
authors.lastname: Gabl
authors.forename: S
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: J
authors.initials: J
authors.lastname: Clausen
authors.forename: G
authors.initials: G
authors.lastname: Gastl
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D015672:Erythroid Precursor Cells / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology