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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1665-1676. Prepublished online as a Blood First Edition Paper on November 21, 2007; DOI 10.1182/blood-2007-09-110601. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-09-110601v1 111/3/1665    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 Ruiz-Vela, A. Articles by Piris, M. A Search for Related Content PubMed PubMed Citation Articles by Ruiz-Vela, A. Articles by Piris, M. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 5, 2007 Accepted November 17, 2007 Lentiviral (HIV)-based RNA interference screen in human B-cell receptor regulatory networks reveals MCL1-induced oncogenic pathways Antonio Ruiz-Vela*, Mohit Aggarwal, Paloma de la Cueva, Cezary Treda, Beatriz Herreros, Daniel Martin-Perez, Orlando Dominguez, and Miguel A Piris Lymphoma Group, Department of Molecular Pathology, Spanish National Cancer Centre (CNIO), Madrid, Spain Genomic Unit, Biotechnology Program, CNIO, Madrid, Spain * Corresponding author; email: antonio.ruizvela{at}universia.es. Aberrant inhibition of B-cell receptor (BCR)-induced programmed cell death pathways is frequently associated with the development of human auto-reactive B-cell lymphomas. Here, we integrated loss-of-function, genomic and bioinformatics approaches for the identification of oncogenic mechanims linked to the inhibition of BCR-induced clonal deletion pathways in human B-cell lymphomas. Lentiviral (HIV)-based RNA interference screen identified MCL1 as a key survival molecule linked to BCR signaling. Loss of MCL1 by RNA interference rendered human B-cell lymphomas sensitive to BCR-induced programmed cell death. Conversely, MCL1 over-expression blocked programmed cell death upon BCR stimulation. To get insight into the mechanisms of MCL1-induced survival and transformation, we screened 41,000 human genes in a genome-wide gene expression profile analysis of MCL1-overexpressing B-cell lymphomas. Bioinformatic gene network reconstruction illustrated reprogramming of relevant oncoproteins within -catenin-TCF signaling pathways induced by enforced MCL1 expression. Overall, our findings not only illustrate MCL1 as an aberrantly expressed reprogramming oncoprotein in follicular lymphomas, but also highlight MCL1 as key therapeutic target. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Pepper, T. T. Lin, G. Pratt, S. Hewamana, P. Brennan, L. Hiller, R. Hills, R. Ward, J. Starczynski, B. Austen, et al. Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers Blood, November 1, 2008; 112(9): 3807 - 3817. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020