|
|
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.
 Previous Article | Next Article 
Submitted July 20, 2006
Accepted November 11, 2006
IRF-4 and c-Rel expression in antiviral resistant adult T-cell leukemia/lymphoma
Juan Carlos Ramos, Phillip Ruiz, Jr., Lee Ratner, Isildinha M Reis, Carlos Brites, Celia Pedroso, Gerald E. Byrne, Jr., Ngoc L Toomey, Valentine Andela, Edward W Harhaj, Izidore Lossos, and William J Harrington, Jr.*
Division of Hematology/Oncology, Dept of Medicine, University of Miami Miller School of Medicine, Miami, FL, United States
Dept of Pathology, University of Miami Miller School of Medicine, Miami, FL, United States
Division of Oncology, Dept of Medicine, Washington University, St. Louis, MO, United States
Division of Biostatistics, Dept of Epidemiology & Public Health, University of Miami Miller School of Medicine, Miami, FL, United States
Division of Infectious Diseases, Dept of Medicine, Federal University of Bahia, Salvador, Brazil
Dept of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, United States
* Corresponding author; email: wharring{at}med.miami.edu.
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. More resistant tumors exhibited c-Rel (6/10 = 60%) as compared to sensitive variants (1/9 = 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 of 11 (91%) non-responders and all c-Rel+ tumors tested and occurred in the absence of the HTLV-I oncoprotein Tax. In contrast, tumors from 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 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:
|
|
|
|
 
K. Tsukasaki, O. Hermine, A. Bazarbachi, L. Ratner, J. C. Ramos, W. Harrington Jr, D. O'Mahony, J. E. Janik, A. L. Bittencourt, G. P. Taylor, et al.
Definition, Prognostic Factors, Treatment, and Response Criteria of Adult T-Cell Leukemia-Lymphoma: A Proposal From an International Consensus Meeting
J. Clin. Oncol.,
January 20, 2009;
27(3):
453 - 459.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
