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

• Published in: The Lancet (British edition) Vol. 355; no. 9216; pp. 1688 - 1691
• Main Authors: Gunsilius, Eberhard, Duba, Hans-Christoph, Petzer, Andreas L, Kahler, Christian M, Grunewald, Kurt, Stockhammer, Gunther, Gabl, Christoph, Dirnhofer, Stephan, Clausen, Johannes, Gastl, Gunther
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 13-05-2000; Lancet; Elsevier Limited
• Subjects: Adult; Biological and medical sciences; Bone marrow; Bone Marrow - pathology; Cells; Endothelium, Vascular - pathology; Erythroid Precursor Cells - pathology; Hematologic and hematopoietic diseases; Hematopoietic Stem Cells - pathology; Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical research; Medical sciences; Middle Aged; Neoplastic Stem Cells - pathology; Human; Molecular hybridization; Endothelial cell; Pathogenesis; In situ; Male; Malignant hemopathy; Gene expression; Endothelium; Case study; Myeloproliferative syndrome; Angiogenesis; Chronic; Blood vessel; Chronic myelocytic leukemia; Bone marrow; Genetics; Molecular biology
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(00)02241-8

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.
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.
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.
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.