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targeting htlv-1 activation of nfκb in mouse models and atll patients针对htlv 1激活nfκb在小鼠模型和atll病人.pdf

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targeting htlv-1 activation of nfκb in mouse models and atll patients针对htlv 1激活nfκb在小鼠模型和atll病人

Viruses 2011, 3, 886-900; doi:10.3390/v3060886 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Targeting HTLV-1 Activation of NFκB in Mouse Models and ATLL Patients Daniel A. Rauch and Lee Ratner * Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Campus Box 8069, 660 S. Euclid Ave., St. Louis, MO 63110, USA; E-Mail: drauch@ * Author to whom correspondence should be addressed; E-Mail: lratner@; Tel.: +1-314-362-8836; Fax: +1-314-747-2120. Received: 27 April 2011; in revised form: 7 June 2011 / Accepted: 9 June 2011 / Published: 21 June 2011 Abstract: Of the millions of HTLV-1 infected carriers worldwide, 3–5% will develop an aggressive T-cell neoplasm that is highly refractory to conventional therapy. The virus carries the Tax oncogene which constitutively activates the NFκB pathway. This co-option of signaling through NFκB provides for the HTLV-1 infected cell an escape from cell cycle arrest and apoptosis, a steady source of growth factors, and a mechanism by which the virus can activate its own target cell. Therapies that target the NFκB pathway sensitize adult T-cell leukemia/lymphoma (ATLL) cells to apoptosis. A focus on translational interrogation of NFκB inhibitors in animal models and ATLL patients is needed to advance NFκB-targeted ATLL therapies to the bedside. Keywords: HTLV-1; tax; NFκB; mouse models; ATLL therapy 1. Introduction Of the 15–2