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

被引：29

作者：

Nasr, Rihab ^{[1
]}

El Hajj, Hiba ^{[2
]}

Kfoury, Youmna ^{[2
]}

de The, Hugues ^{[3
]}

Hermine, Olivier ^{[4
]}

Bazarbachi, Ali ^{[2
]}

机构：

[1] Amer Univ Beirut, Dept Anat Cell Biol & Physiol Sci, Fac Med, Beirut 11072020, Lebanon

[2] Amer Univ Beirut, Dept Internal Med, Fac Med, Beirut 11072020, Lebanon

[3] Univ Paris Diderot, Serv Biochim, Equipe Labellisee, Ligue Natl Canc,CNRS,INSERM,Unite Mixte Rech 7212, F-75475 Paris 10, France

[4] Univ Paris 05, Serv Hematol, Equipe Labellisee, Ligue Natl Canc,CNRS,Unite Mixte Rech 8147,Hop Ne, F-75015 Paris 15, France

来源：

VIRUSES-BASEL | 2011年 / 3卷 / 06期

关键词：

adult T cell leukemia; HTLV-I; Tax; AZT; arsenic trioxide; interferon; VIRUS TYPE-I; HTLV-1 PROVIRAL LOAD; NF-KAPPA-B/REL; LEUKEMIA-VIRUS; INTERFERON-ALPHA; ARSENIC TRIOXIDE; TAX PROTEIN; TYPE-1; TAX; SUMOYLATION CONTROL; TRANSFORMED-CELLS;

D O I：

10.3390/v3060750

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：750 / 769

页数：20

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