CD62L as a therapeutic target in chronic lymphocytic leukemia.
OBJECTIVE
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.


METHODS
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 CD5(+)/CD19(+) 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.


CONCLUSIONS
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 patients with CLL receiving current standard chemotherapy protocols.
Authors' Affiliations: University of Queensland Diamantina Institute, Brisbane, Australia; Department of Haematology, Princess Alexandra Hospital, Brisbane, Australia; Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida; and Griffith Health Institute and School of Medical Sciences, Griffith University, Southport, Queensland, Australia.
Melinda
M
Burgess
Devinder
D
Gill
Richa
R
Singhania
Catherine
C
Cheung
Lynne
L
Chambers
Brent A
BA
Renyolds
Louise
L
Smith
Peter
P
Mollee
Nicholas
N
Saunders
Nigel Aj
NA
McMillan
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D019041:L-Selectin