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Blood, 15 January 2006, Vol. 107, No. 2, pp. 689-697. Prepublished online as a Blood First Edition Paper on September 27, 2005; DOI 10.1182/blood-2005-05-2125. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-05-2125v1 107/2/689    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 Piva, R. Articles by Inghirami, G. Search for Related Content PubMed PubMed Citation Articles by Piva, R. Articles by Inghirami, G. Related Collections Neoplasia Apoptosis Cell Cycle Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Ablation of oncogenic ALK is a viable therapeutic approach for anaplastic large-cell lymphomas Roberto Piva, Roberto Chiarle, Andrea D. Manazza, Riccardo Taulli, William Simmons, Chiara Ambrogio, Valentina D'Escamard, Elisa Pellegrino, Carola Ponzetto, Giorgio Palestro, and Giorgio Inghirami From the Departments of Pathology and Anatomy, and the Center for Experimental Research and Medical Studies (CeRMS), University of Turin, Italy; and the Department of Pathology and the NYU Cancer Center, New York University School of Medicine, New York, NY. Anaplastic large-cell lymphomas (ALCLs) carry chromosome translocations in which the anaplastic lymphoma kinase (ALK) gene is fused to several partners, most frequently, the NPM1 gene. We have demonstrated that the constitutive activation of ALK fusion proteins results in cellular transformation and lymphoid neoplasia. Herein, we specifically down-regulated ALK protein expression by using small hairpin RNA (shRNA) targeting a sequence coding for the catalytic domain of ALK. The ablation of ALK leads to the down-modulation of known ALK downstream effectors, cell growth arrest, and reversion of the transformed phenotype of ALK+ mouse embryonic fibroblasts in vitro and in vivo. In human ALCL cells lentiviral-mediated ALK knock-down leads to G1 cell-cycle arrest and apoptosis in vitro and tumor growth inhibition and regression in vivo. Using a specific approach we have demonstrated that the survival and growth of ALK+ ALCLs are strictly dependent on ALK activation and signaling. Therefore, ALK is a viable target for therapeutic intervention and its inactivation might represent a pivotal approach for the treatment of ALK lymphomas and other ALK-dependent human tumors. 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