Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia

Leukemia. 2010 Sep;24(9):1588-98. doi: 10.1038/leu.2010.152. Epub 2010 Jul 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Acylation
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Cytokines / metabolism
  • DNA Primers
  • Female
  • Humans
  • Immunophenotyping
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Toll-Like Receptors / metabolism
  • Tumor Cells, Cultured


  • Cytokines
  • DNA Primers
  • Toll-Like Receptors
  • Acetylglucosamine