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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1801-1807. Prepublished online as a Blood First Edition Paper on May 10, 2005; DOI 10.1182/blood-2004-11-4513. This Article Full Text (PDF) All Versions of this Article: 2004-11-4513v1 106/5/1801    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 Jundt, F. Articles by Dorken, B. Search for Related Content PubMed PubMed Citation Articles by Jundt, F. Articles by Dorken, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 30, 2004 Accepted May 1, 2005 A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein and NF-B activity in Hodgkin and anaplastic large cell lymphomas Franziska Jundt*, Nina Raetzel, Christine Muller, Cornelis F Calkhoven, Katharina Kley, Stephan Mathas, Andreas Lietz, Achim Leutz, and Bernd Dorken Department of Hematology and Oncology, Charite, Campus Virchow-Klinikum, University Medicine, Berlin, Germany; Max Delbruck Center for Molecular Medicine, Berlin, Germany Department of Hematology and Oncology, Charite, Campus Virchow-Klinikum, University Medicine, Berlin, Germany Max Delbruck Center for Molecular Medicine, Berlin, Germany * Corresponding author; email: fjundt{at}mdc-berlin.de. The immunosuppressive macrolide rapamycin and its derivate SDZ RAD (RAD, everolimus) inhibit the mammalian target of rapamycin (mTOR) signaling pathway. In this study, we provide evidence that RAD has profound anti-proliferative activity in vitro and in NOD/SCID mice in vivo against Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) cells. Moreover, we identified two molecular mechanisms that showed how RAD exerts anti-proliferative effects in HL and ALCL cells. RAD down-regulated the truncated isoform of the transcription factor CCAAT enhancer binding protein (C/EBP), that is known to disrupt terminal differentiation and induce a transformed phenotype. Furthermore, RAD inhibited constitutive NF-B activity, that is a critical survival factor of HL cells. Pharmacological inhibition of the mTOR pathway by RAD therefore interferes with essential proliferation and survival pathways in HL and ALCL cells and might serve as a novel treatment option. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Rodriguez, E. Conde, A. Gutierrez, J. J. Lahuerta, R. Arranz, A. Sureda, J. Zuazu, A. F. de Sevilla, M. Bendandi, C. Solano, et al. The adjusted International Prognostic Index and {beta}-2-microglobulin predict the outcome after autologous stem cell transplantation in relapsing/refractory peripheral T-cell lymphoma Haematologica, August 1, 2007; 92(8): 1067 - 1074. [Abstract] [Full Text] [PDF] L. Lamant, A. d. Reynies, M.-M. Duplantier, D. S. Rickman, F. Sabourdy, S. Giuriato, L. Brugieres, P. Gaulard, E. Espinos, and G. Delsol Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes Blood, March 1, 2007; 109(5): 2156 - 2164. [Abstract] [Full Text] [PDF] M. Jankiewicz, B. Groner, and S. Desrivieres Mammalian Target of Rapamycin Regulates the Growth of Mammary Epithelial Cells through the Inhibitor of Deoxyribonucleic Acid Binding Id1 and Their Functional Differentiation through Id2 Mol. Endocrinol., October 1, 2006; 20(10): 2369 - 2381. [Abstract] [Full Text] [PDF] K. W.L. Yee, Z. Zeng, M. Konopleva, S. Verstovsek, F. Ravandi, A. Ferrajoli, D. Thomas, W. Wierda, E. Apostolidou, M. Albitar, et al. Phase I/II Study of the Mammalian Target of Rapamycin Inhibitor Everolimus (RAD001) in Patients with Relapsed or Refractory Hematologic Malignancies Clin. Cancer Res., September 1, 2006; 12(17): 5165 - 5173. [Abstract] [Full Text] [PDF] V. Wiesenthal, A. Leutz, and C. F. Calkhoven A translation control reporter system (TCRS) for the analysis of translationally controlled processes in the vertebrate cell Nucleic Acids Res., February 10, 2006; 34(3): e23 - e23. [Abstract] [Full Text] [PDF]

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