Journal
EXPERIMENTAL HEMATOLOGY
Volume 41, Issue 8, Pages 675-686Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.exphem.2013.04.004
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Funding
- Harold E. Johns Studentship award of the Terry Fox Foundation
- Canadian Institutes of Health Research [190633]
- Leukemia and Lymphoma Society of Canada
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CLL cells are characterized by high levels of proteins that are post-translationally modified by O-linked beta-N-acetylglucosamine (O-GlcNAc) moieties, but it is not clear whether O-GlcNAc is a relevant therapeutic target. The neutraceutical resveratrol is cytotoxic to chronic lymphocytic leukemia cells in vitro. In this study, we found that resveratrol has therapeutic activity as a single agent in vivo in both human chronic lymphocytic leukemia patients and mice with erythroleukemia. Blood and splenic O-GlcNAc levels reflected the changes in tumor burden. Resveratrol directly lowered O-GlcNAc levels in leukemia cells through proteasomal activation, but increasing O-GlcNAc levels in vitro did not prevent cell death. These findings suggest that resveratrol has potential as a novel treatment for some forms of chronic and acute leukemia, and the measurement of O-GlcNAc levels could be a surrogate marker for therapeutic responses. (c) 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
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