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

Br J Haematol. 2001 Dec;115(4):862-71. doi: 10.1046/j.1365-2141.2001.03182.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis
  • Bone Marrow Cells / physiology*
  • Cell Adhesion
  • Cell Line
  • Cell Survival
  • Cells, Cultured
  • Child
  • Humans
  • Intercellular Adhesion Molecule-1 / pharmacology*
  • Leukemia-Lymphoma, Adult T-Cell / pathology*
  • Lymphocyte Function-Associated Antigen-1 / pharmacology*
  • Protein Binding
  • Stromal Cells / physiology*


  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1