Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells.
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.
Gunsilius
E
E
Division of Haematology and Oncology, University of Innsbruck, Austria. eberhard.gunsilius@uibk.ac.at
Duba
H C
HC
Petzer
A L
AL
Kähler
C M
CM
Grünewald
K
K
Stockhammer
G
G
Gabl
C
C
Dirnhofer
S
S
Clausen
J
J
Gastl
G
G
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