ACUTE MYELOID-LEUKEMIA BLAST CELLS BIND TO HUMAN ENDOTHELIUM IN-VITROUTILIZING E-SELECTIN AND VASCULAR CELL-ADHESION MOLECULE-1 (VCAM-1)

The adhesion of acute myeloid leukaemia (AML) blast cells to human umb ilical vein endothelial cells (HUVECs) was investigated in vitro. Adhe sion of blast cells from 10 cases of AML to unstimulated and interleuk in-1beta (IL-1) stimulated HUVECs was similar to or greater than that of control neutrophils. The extent to which endothelial E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were involved in this adhe sive process was investigated using blocking monoclonal antibodies to these proteins. In the majority of cases studied (7/8), anti-E-selecti n significantly inhibited adhesion to IL-1 stimulated endothelium (26- 65% inhibition) and in 5/8 cases so did anti-VCAM-1 (maximum of 31% in hibition). All cases were found to express the sialylated Lewis x anti gen and very late activation antigen-4, ligands for E-selectin and VCA M-1 respectively. Our results indicate that leukaemic blast cells adhe re to human endothelium and that there are E-selectin and, to a lesser extent, VCAM-1-dependent components to this process. Such adhesive in teractions are likely to confer on AML blast cells the ability to migr ate across the vascular wall and so to establish extravascular disease .