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

Background Vascular endothelial cells lost from the blood-vessel endotheliu m through necrosis or apoptosis must be replaced. We investigated in a leuk aemia model whether bone-marrow-derived endothelial cells contribute to thi s maintenance angiogenesis. Methods We studied six patients with chronic myelogenous leukaemia (CML) ca rrying the BCR/ABL fusion gene in their bone-marrow-derived cells. We scree ned endothelial cells generated in vitro from bone-marrow-derived progenito r cells and vascular endothelium in myocardial tissue for the BCR/ABL fusio n gene by in-situ hybridisation. For detection of donor-type endothelial ce lls 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 (0-5 6%) of endothelial cells generated in vitro. Endothelial cells expressing t he fusion gene were found in the vascular endothelium of a patient. In a re cipient of an allogeneic stem-cell transplant, normal donor-type endothelia l cells were detected in the Vascular endothelium. Interpretation These findings suggest that CML is not solely a haematologic al disease but originates from a bone-marrow-derived haemangioblastic precu rsor cell that can give rise to both blood cells and endothelial cells. Mor eover, normal bone-marrow-derived endothelial cells can contribute to the m aintenance of the blood vascular endothelium. The integration of bone-marro w-derived endothelial cells into the vascular endothelium provides a ration ale for developing vascular targeting strategies in vasculopathies, inflamm atory diseases, and cancer.