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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 16, 2008 Accepted September 25, 2008 A peptomimetic inhibitor of BCL6 with potent anti-lymphoma effects in vitro and in vivo Leandro C Cerchietti, Shao Ning Yang, Rita Shaknovich, Katerina Hatzi, Jose M Polo, Amy Chadburn, Steven F Dowdy, and Ari Melnick* Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, United States Department of Pathology, Weill Cornell College of Medicine, New York, NY, United States Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, United States Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California at San Diego School of Medicine, La Jolla, CA, United States * Corresponding author; email: amm2014{at}med.cornell.edu. The BCL6 transcriptional repressor is the most commonly involved oncogene in diffuse large B-cell lymphomas (DLBCL). 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 corepressor that blocks this site can inhibit BCL6 biological functions. Shortening and conversion of this peptide to D-amino acid and retro configuration, and 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, RI-BPI (Retro-Inverso BCL6 Peptide Inhibitor) 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 non-toxic and non-immunogenic 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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