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ABSTRACT 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

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our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS METABOLIC REPROGRAMMING REGULATED BY TRAF6 CONTRIBUTES TO THE LEUKEMIA PROGRESSION Article Open access 12 April

2024 ACOX1-MEDIATED PEROXISOMAL FATTY ACID OXIDATION CONTRIBUTES TO METABOLIC REPROGRAMMING AND SURVIVAL IN CHRONIC LYMPHOCYTIC LEUKEMIA Article 06 December 2023 ABERRANT BCAT1 EXPRESSION

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work was supported by Grants from the Ontario Institute of Cancer Research (OICR no. 07Nov-61)), the Canadian Institutes of Health Research (CIHR) (no. 190633) and the Leukemia and Lymphoma

Society of Canada (to DS), a Camille Dreyfus Teacher-Scholar award (no. TC-03-009) (to SW), CIHR Grants MOP-79405 and MOP-43938 and a Grant from Genome Canada through the Ontario Genomics

Institute (to JWD), Grants NCI R01CA42486 and NIDDK R01 DK61671 (to GWH) and CIHR Grant no. 15095 (to JPD). We thank Dimitar Efremov, Mark Minden and Suzanne Kamel-Reid for helpful

discussions. AUTHOR INFORMATION Author notes * Y Shi and J Tomic: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Division of Molecular and Cellular Biology,

Research Institute, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada Y Shi, J Tomic, F Wen, S Shaha, A Bahlo, R Harrison & D E Spaner * Department of Medical Biophysics,

University of Toronto, Toronto, Ontario, Canada J Tomic & D E Spaner * Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada J W Dennis & R Williams *

Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA B J Gross & S Walker * Department of Biochemistry and Molecular Biology, Immunology Research

Group, University of Calgary, Calgary, Ontario, Canada J Zuccolo & J P Deans * Department of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore, MD, USA G W

Hart * Department of Medical Oncology, Sunnybrook Odette Cancer Center, Toronto, Ontario, Canada D E Spaner * Department of Medicine, University of Toronto, Toronto, Ontario, Canada D E

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search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to D E Spaner. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest.

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24 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Shi, Y., Tomic, J., Wen, F. _et al._ Aberrant O-GlcNAcylation characterizes chronic lymphocytic

leukemia. _Leukemia_ 24, 1588–1598 (2010). https://doi.org/10.1038/leu.2010.152 Download citation * Received: 31 August 2009 * Revised: 03 June 2010 * Accepted: 21 June 2010 * Published: 29

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shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * chronic

lymphocytic leukemia * glycolysis * hexosamine pathway * signal transduction * glucosamine