Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia

作者：Shi Y; Tomic J; Wen F; Shaha S; Bahlo A; Harrison R; Dennis J W; Williams R; Gross B J; Walker S; Zuccolo J; Deans J P; Hart G W; Spaner D E^*

来源：Leukemia, 2010, 24(9): 1588-1598.

DOI：10.1038/leu.2010.152

• chronic lymphocytic leukemia
• glycolysis
• hexosamine pathway
• signal transduction
• glucosamine

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

• 出版日期2010-9