Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells

E Gunsilius, HC Duba, AL Petzer, CM Kahler… - The Lancet, 2000 - thelancet.com
E Gunsilius, HC Duba, AL Petzer, CM Kahler, K Grunewald, G Stockhammer, C Gabl…
The Lancet, 2000thelancet.com
Background Vascular endothelial cells lost from the bloodvessel 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 …
Background
Vascular endothelial cells lost from the bloodvessel 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.
Findings
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.
Interpretation
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.
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