Journal
LEUKEMIA
Volume 24, Issue 9, Pages 1588-1598Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2010.152
Keywords
chronic lymphocytic leukemia; glycolysis; hexosamine pathway; signal transduction; glucosamine
Categories
Funding
- Ontario Institute of Cancer Research (OICR) [07Nov-61]
- Canadian Institutes of Health Research (CIHR) [190633, MOP-79405, MOP-43938, 15095]
- Leukemia and Lymphoma Society of Canada
- Camille Dreyfus Teacher-Scholar award [TC-03-009]
- Genome Canada through the Ontario Genomics Institute
- NCI [R01CA42486]
- NIDDK [R01 DK61671]
Ask authors/readers for more resources
O-linked N-Acetylglucosamine (O-GlcNAc) post-translational modifications originate from the activity of the hexosamine pathway, and are known to affect intracellular signaling processes. As aberrant responses to microenvironmental signals are a feature of chronic lymphocytic leukemia (CLL), O-GlcNAcylated protein levels were measured in primary CLL cells. In contrast to normal circulating and tonsillar B cells, CLL cells expressed high levels of O-GlcNAcylated proteins, including p53, c-myc and Akt. O-GlcNAcylation in CLL cells increased following activation with cytokines and through toll-like receptors (TLRs), or after loading with hexosamine pathway substrates. However, high baseline O-GlcNAc levels were associated with impaired signaling responses to TLR agonists, chemotherapeutic agents, B cell receptor crosslinking and mitogens. Indolent and aggressive clinical behavior of CLL cells were found to correlate with higher and lower O-GlcNAc levels, respectively. These findings suggest that intracellular O-GlcNAcylation is associated with the pathogenesis of CLL, which could potentially have therapeutic implications. Leukemia (2010) 24, 1588-1598; doi:10.1038/leu.2010.152; published online 29 July 2010
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available