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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2399-2406. Prepublished online as a Blood First Edition Paper on June 15, 2006; DOI 10.1182/blood-2006-04-018556. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-018556v1 108/7/2399    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cabrera, P. V. Articles by Baum, L. G. Search for Related Content PubMed PubMed Citation Articles by Cabrera, P. V. Articles by Baum, L. G. Related Collections Immunobiology Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Haploinsufficiency of C2GnT-I glycosyltransferase renders T lymphoma cells resistant to cell death Paula V. Cabrera, Maho Amano, Junya Mitoma, Jessica Chan, Jonathan Said, Minoru Fukuda, and Linda G. Baum From the Department of Pathology, University of California, School of Medicine, Los Angeles; the Jonsson Comprehensive Cancer Center, University of California, School of Medicine, Los Angeles; and the Glycobiology Program, Cancer Research Center, Burnham Institute, La Jolla, CA. Neoplastic T cells in mycosis fungoides (MF) are resistant to apoptotic agents, including galectin-1 that is abundant in skin. Although MF cells are typically CD7–, and thus galectin-1 resistant, CD7+ HH cells, derived from a patient with MF, were also resistant to galectin-1. HH cells demonstrate altered cell surface glycosylation, with loss of core 2 O-glycan ligands for galectin-1 created by core 2 1,6-N-acetylglucosaminyltransferase (C2GnT-I). Loss of core 2 O-glycans on tumor cells was also seen in primary CD7+ MF lesions. Surprisingly, HH cells are heterozygous for a C2GnT-I point mutation, yet this mutation resulted in a dramatic reduction in cellular glycosyltransferase activity. Expression of wild-type C2GnT-I in human HH cells, or murine lymphoma cells that lack C2GnT-I, restored core 2 O-glycan expression and susceptibility to galectin-1, whereas mutant enzyme lacked activity and did not restore core 2 O-glycan expression or susceptibility to galectin-1. Mutant enzyme did not have a dominant negative effect by affecting dimerization or activity of wild-type enzyme; rather, C2GnT-I haploinsufficiency is sufficient for loss of core 2 O-glycan expression and galectin-1 resistance. Thus, glycosyltransferase haploinsufficiency results in altered cellular glycosylation and resistance to cell death, identifying a new survival mechanism for T-lymphoma cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Bi, L. A. Earl, L. Jacobs, and L. G. Baum Structural Features of Galectin-9 and Galectin-1 That Determine Distinct T Cell Death Pathways J. Biol. Chem., May 2, 2008; 283(18): 12248 - 12258. [Abstract] [Full Text] [PDF] C. Cederfur, E. Salomonsson, J. Nilsson, A. Halim, C. T Oberg, G. Larson, U. J Nilsson, and H. Leffler Different affinity of galectins for human serum glycoproteins: Galectin-3 binds many protease inhibitors and acute phase proteins Glycobiology, May 1, 2008; 18(5): 384 - 394. [Abstract] [Full Text] [PDF] H. F. Valenzuela, K. E. Pace, P. V. Cabrera, R. White, K. Porvari, H. Kaija, P. Vihko, and L. G. Baum O-Glycosylation Regulates LNCaP Prostate Cancer Cell Susceptibility to Apoptosis Induced by Galectin-1 Cancer Res., July 1, 2007; 67(13): 6155 - 6162. [Abstract] [Full Text] [PDF] S. Carlsson, C. T Oberg, M. C Carlsson, A. Sundin, U. J Nilsson, D. Smith, R. D Cummings, J. Almkvist, A. Karlsson, and H. Leffler Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface Glycobiology, June 1, 2007; 17(6): 663 - 676. [Abstract] [Full Text] [PDF]

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