Haematologica (Apr 2012)

AMD3100 disrupts the cross-talk between chronic lymphocytic leukemia cells and a mesenchymal stromal or nurse-like cell-based microenvironment: pre-clinical evidence for its association with chronic lymphocytic leukemia treatments

  • Basile Stamatopoulos,
  • Nathalie Meuleman,
  • Cécile De Bruyn,
  • Karlien Pieters,
  • Philippe Mineur,
  • Christine Le Roy,
  • Stéphane Saint-Georges,
  • Nadine Varin-Blank,
  • Florence Cymbalista,
  • Dominique Bron,
  • Laurence Lagneaux

DOI
https://doi.org/10.3324/haematol.2011.052779
Journal volume & issue
Vol. 97, no. 4

Abstract

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Background Interactions with the microenvironment, such as bone marrow mesenchymal stromal cells and nurse-like cells, protect chronic lymphocytic leukemia cells from spontaneous and drug-induced apoptosis. This protection is partially mediated by the chemokine SDF-1α (CXCL12) and its receptor CXCR4 (CD184) present on the chronic lymphocytic leukemia cell surface.Design and Methods Here, we investigated the ability of AMD3100, a CXCR4 antagonist, to sensitize chronic lymphocytic leukemia cells to chemotherapy in a chronic lymphocytic leukemia/mesenchymal stromal cell based or nurse-like cell based microenvironment co-culture model.Results AMD3100 decreased CXCR4 expression signal (n=15, P=0.0078) and inhibited actin polymerization/migration in response to SDF-1α (n=8, P