title: Controversies in targeted therapy of adult T cell leukemia/lymphoma: ON target or OFF target effects?
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.
authors: Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107 2020, Lebanon. rn03@aub.edu.lb
authors: Rihab
authors: R
authors: Nasr
authors: Hiba
authors: H
authors: El Hajj
authors: Youmna
authors: Y
authors: Kfoury
authors: Hugues
authors: H
authors: de Thé
authors: Olivier
authors: O
authors: Hermine
authors: Ali
authors: A
authors: Bazarbachi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D016356:Gene Products, tax / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000821:virology; D051379:Mice; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016356:Gene Products, tax; C514970:tax protein, Human T-lymphotrophic virus 1