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Blood, 1 April 2007, Vol. 109, No. 7, pp. 3060-3068. Prepublished online as a Blood First Edition Paper on November 30, 2006; DOI 10.1182/blood-2006-07-036368. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-036368v1 109/7/3060    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 Ramos, J. C. Articles by Harrington, W. J. Search for Related Content PubMed PubMed Citation Articles by Ramos, J. C. Articles by Harrington, W. J., Jr Related Collections Neoplasia Oncogenes and Tumor Suppressors Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma Juan Carlos Ramos1, Phillip Ruiz, Jr2, Lee Ratner3, Isildinha M. Reis4, Carlos Brites5, Celia Pedroso5, Gerald E. Byrne, Jr2, Ngoc L. Toomey1, Valentine Andela1, Edward W. Harhaj6, Izidore S. Lossos1, and William J. Harrington, Jr1 1 Division of Hematology/Oncology, Department of Medicine, 2 Department of Pathology, 4 Division of Biostatics, Department of Epidemiology and Public Health, and 6 Department of Microbiology and Immunology, University of Miami Miller School of Medicine, FL; 3 Division of Oncology, Department of Medicine, Washington University, St Louis, MO; 5 Division of Infectious Disease, Department of Medicine, Federal University of Bahia, Salvador, Brazil Adult T-cell leukemia/lymphoma (ATLL) is a generally fatal malignancy. Most ATLL patients fare poorly with conventional chemotherapy; however, antiviral therapy with zidovudine (AZT) and interferon alpha (IFN-) has produced long-term clinical remissions. We studied primary ATLL tumors and identified molecular features linked to sensitivity and resistance to antiviral therapy. Enhanced expression of the proto-oncogene c-Rel was noted in 9 of 27 tumors. Resistant tumors exhibited c-Rel (6 of 10; 60%) more often than did sensitive variants (1 of 9; 11%). This finding was independent of the disease form. Elevated expression of the putative c-Rel target, interferon regulatory factor-4 (IRF-4), was observed in 10 (91%) of 11 nonresponders and in all tested patients with c-Rel+ tumors and occurred in the absence of the HTLV-1 oncoprotein Tax. In contrast, tumors in complete responders did not express c-Rel or IRF-4. Gene rearrangement studies demonstrated the persistence of circulating T-cell clones in long-term survivors maintained on antiviral therapy. The expression of nuclear c-Rel and IRF-4 occurs in the absence of Tax in primary ATLL and is associated with antiviral resistance. These molecular features may help guide treatment. AZT and IFN- is a suppressive rather than a curative regimen, and patients in clinical remission should remain on maintenance therapy indefinitely. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W.-L. Zhao, Y.-Y. Liu, Q.-L. Zhang, L. Wang, C. Leboeuf, Y.-W. Zhang, J. Ma, J.-F. Garcia, Y.-P. Song, J.-M. Li, et al. PRDM1 is involved in chemoresistance of T-cell lymphoma and down-regulated by the proteasome inhibitor Blood, April 1, 2008; 111(7): 3867 - 3871. [Abstract] [Full Text] [PDF]

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