CD62L as a therapeutic target in chronic lymphocytic leukemia
Menée in vitro, cette étude suggère l'intérêt d'anticorps anti CD62L, en combinaison avec une chimiothérapie standard, pour le traitement des patients atteints d'une leucémie lymphocytaire chronique
Purpose: Despite advances in the treatment of chronic lymphocytic leukemia (CLL), the disease remains incurable with standard therapies and relapse is inevitable. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of CLL. Experimental Design: The expression of 71 cell surface molecules was examined on CLL PBMCs over 3 weeks in culture. The most highly up-regulated marker, CD62L, was examined further for expression on CD5+/CD19+ CLL cells in vitro and in lymph node and bone marrow biopsies. The pro-survival role of CD62L was examined using a functional blocking antibody and therapeutic potential evaluated by comparison with current chemotherapy agents. Results: Blocking CD62L resulted in apoptosis of CLL cells but not peripheral blood mononuclear cells (PBMCs) from healthy donors suggesting a novel role for CD62L in CLL cell survival. The beneficial effect of co-culturing CLL cells with bone marrow stromal cells or endothelial cells does not protect CLL cells from anti-CD62L related toxicity. Moreover, combining fludarabine or mafosfamide with the anti-CD62L in vitro produced an additive effect both with and without stromal cells. Conclusion: This is the first reported data showing that blocking the activation and homing marker, CD62L, regulates CLL cell survival in vitro. These data also suggest that therapeutic antibodies against CD62L may provide additional clinical benefit to CLL patients receiving current standard chemotherapy protocols.