CD62L as a therapeutic target in chronic lymphocytic leukemia

Burgess, Melinda, Gill, Devinder, Singhania, Richa, Cheung, Catherine, Chambers, Lynne, Renyolds, Brent A., Smith, Louise, Mollee, Peter, Saunders, Nicholas and McMillan, Nigel A. J. (2013) CD62L as a therapeutic target in chronic lymphocytic leukemia. Clinical Cancer Research, 19 20: 5675-5685. doi:10.1158/1078-0432.CCR-13-1037

Author Burgess, Melinda
Gill, Devinder
Singhania, Richa
Cheung, Catherine
Chambers, Lynne
Renyolds, Brent A.
Smith, Louise
Mollee, Peter
Saunders, Nicholas
McMillan, Nigel A. J.
Title CD62L as a therapeutic target in chronic lymphocytic leukemia
Journal name Clinical Cancer Research   Check publisher's open access policy
ISSN 1078-0432
Publication date 2013-10-01
Year available 2013
Sub-type Article (original research)
DOI 10.1158/1078-0432.CCR-13-1037
Open Access Status Not Open Access
Volume 19
Issue 20
Start page 5675
End page 5685
Total pages 11
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Formatted abstract
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 peripheral blood mononuclear cells (PBMCs) over 3 weeks in culture. The most highly upregulated marker, CD62L, was examined further for expression on CD5þ/CD19þ CLL cells in vitro and in lymph node and bone marrow biopsies. The prosurvival 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 PBMCs from healthy donors suggesting a novel role for CD62L in CLL cell survival. The beneficial effect of coculturing 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 survivalin vitro.These data also suggest that therapeutic antibodies against CD62L may provide additional clinical benefit to patients with CLL receiving current standard chemotherapy protocols.
Keyword B-Cell Receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
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