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Blood, 9 April 2009, Vol. 113, No. 15, pp. 3397-3405. Prepublished online as a Blood First Edition Paper on October 16, 2008; DOI 10.1182/blood-2008-07-168773. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-07-168773v1 113/15/3397    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 Cerchietti, L. C. Articles by Melnick, A. Search for Related Content PubMed PubMed Citation Articles by Cerchietti, L. C. Articles by Melnick, A. Related Collections Plenary Papers Lymphoid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER A peptomimetic inhibitor of BCL6 with potent antilymphoma effects in vitro and in vivo Leandro C. Cerchietti1, Shao Ning Yang1, Rita Shaknovich2, Katerina Hatzi1, Jose M. Polo3, Amy Chadburn2, Steven F. Dowdy4, and Ari Melnick1 1 Division of Hematology and Medical Oncology, Department of Medicine, and 2 Department of Pathology, Weill Cornell College of Medicine, New York, NY; 3 Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY; and 4 Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California at San Diego School of Medicine, La Jolla The BCL6 transcriptional repressor is the most commonly involved oncogene in diffuse large B-cell lymphomas (DLBCLs). BCL6 lymphomagenic activity is dependent on its ability to recruit corepressor proteins to a unique binding site on its N-terminal BTB domain. A recombinant peptide fragment of the SMRT (silencing mediator for retinoid and thyroid hormone receptor) corepressor that blocks this site can inhibit BCL6 biologic functions. Shortening and conversion of this peptide to D-amino acid and retro configuration as well as the addition of a fusogenic motif yielded a far more potent and stable BCL6 inhibitor that still retained the specificity of the original SMRT fragment. Like the L-peptide, retroinverso BCL6 peptide inhibitor (RI-BPI) selectively killed BCR rather than OxPhos-type DLBCL cells. The RI-BPI could recapitulate the failure to form germinal centers seen in BCL6 null mice yet was nontoxic and nonimmunogenic even when administered for up to 52 weeks. RI-BPI showed superior duration of tissue penetration and could accordingly powerfully suppress the growth of human DLBCLs xenografts in a dose-dependent manner. Finally, RI-BPI could kill primary human DLBCL cells but had no effect on normal lymphoid tissue or other tumors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Going retro on lymphoma Alexander L. Dent Blood 2009 113: 3393-3394. [Full Text] [PDF] This article has been cited by other articles: W. Ci, J. M. Polo, L. Cerchietti, R. Shaknovich, L. Wang, S. N. Yang, K. Ye, P. Farinha, D. E. Horsman, R. D. Gascoyne, et al. The BCL6 transcriptional program features repression of multiple oncogenes in primary B cells and is deregulated in DLBCL Blood, May 28, 2009; 113(22): 5536 - 5548. [Abstract] [Full Text] [PDF] A. L. Dent Going retro on lymphoma Blood, April 9, 2009; 113(15): 3393 - 3394. [Full Text] [PDF]

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