Enhanced T‐lineage acute lymphoblastic leukaemia cell survival on bone marrow stroma requires involvement of LFA‐1 and ICAM‐1

The bone marrow (BM) microenvironment supports leukaemia cell survival and proliferation. The roles played by adhesive receptor interactions in the survival of T‐lineage acute lymphoblastic leukaemia (T‐ALL) cells on BM stromal cells are not well understood. Recently, we have developed an assay that partially recapitulates the BM microenvironment using HS‐5 BM stromal cells. In this assay, the magnitude of ex vivo T‐ALL lymphoblast survival predicts patient outcome. We examined the molecular basis for cell–cell adhesive events leading to T‐ALL lymphoblast survival on HS‐5 and on donor‐derived BM stroma. Lympho cyte function‐associated antigen‐1 (LFA‐1) on T‐ALL cell lines bound intercellular adhesion molecule‐1 (ICAM‐1) on HS‐5 monolayers, and survival was inhibited 85–98% with monoclonal antibodies directed against LFA‐1 or ICAM‐1. We compared these results with patient‐derived T‐ALL lymphoblasts co‐cultured on either HS‐5 BM or normal BM monolayers and found that LFA‐1 and ICAM‐1 were required, but not alone sufficient for ex vivo leukaemic cell survival. On normal BM stroma, but not HS‐5 monolayers, two additional adhesion molecules, vascular cell adhesion molecule‐1 (VCAM‐1) and E‐selectin, were highly expressed and contributed to T‐ALL cell survival. This is the first report to demonstrate the importance of LFA‐1/ICAM‐1‐mediated adhesion as a critical event in a cascade of cell surface receptor–ligand interactions that regulate T‐ALL survival in the BM microenvironment.