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Viruses 2011, 3(6), 750-769; doi:10.3390/v3060750
Review

Controversies in Targeted Therapy of Adult T Cell Leukemia/Lymphoma: ON Target or OFF Target Effects?

1,* , 2
, 2
, 3
, 4
 and 2,*
1 Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon 2 Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon 3 Service de Biochimie, Equipe labellisée, Ligue Nationale Contre le Cancer, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Paris Diderot Unité Mixte de Recherche 7212, Unité 944, Hôpital Saint Louis, 75475 Paris, Cedex 10, France 4 Service d’hématologie, Equipe labellisée, Ligue Nationale Contre le Cancer, Centre National de la Recherche Scientifique, Université Paris Descartes Unité Mixte de Recherche 8147, Hôpital Necker-Enfants Malades, 75015 Paris, Cedex 15, France
* Authors to whom correspondence should be addressed.
Received: 8 April 2011 / Revised: 16 May 2011 / Accepted: 17 May 2011 / Published: 14 June 2011
(This article belongs to the Special Issue Recent Developments in HTLV Research)
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Abstract

Adult T cell leukemia/lymphoma (ATL) represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT) and interferon-alpha (IFN) has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT) and Tax degradation (arsenic/IFN) are needed to cure ATL.
Keywords: adult T cell leukemia; HTLV-I; Tax; AZT; arsenic trioxide; interferon adult T cell leukemia; HTLV-I; Tax; AZT; arsenic trioxide; interferon
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Nasr, R.; Hajj, H.E.; Kfoury, Y.; Thé, H.; Hermine, O.; Bazarbachi, A. Controversies in Targeted Therapy of Adult T Cell Leukemia/Lymphoma: ON Target or OFF Target Effects? Viruses 2011, 3, 750-769.

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