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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia
Journal of Experimental Medicine, Volume 207, No. 13, Year 2010
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Description
Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As2O3 and IFN-α combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients. © 2010 El Hajj et al.
Authors & Co-Authors
El Hajj, Hiba
Lebanon, Beirut
American University of Beirut
El-Sabban, Marwan
Lebanon, Beirut
American University of Beirut
Hasegawa, Hideki
Japan, Tokyo
National Institute of Infectious Diseases
Ireland, Dublin
University College Dublin
Zaatari, Ghazi
Lebanon, Beirut
American University of Beirut
Ablain, Julien
France, Paris
Génomes, Biologie Cellulaire et Thérapeutique
Saab, Shahrazad T.
Lebanon, Beirut
American University of Beirut
Janin, Anne
France, Paris
Hôpital Saint-louis
Mahfouz, Rami
Lebanon, Beirut
American University of Beirut
Nasr, Rihab
Lebanon, Beirut
American University of Beirut
Kfoury, Youmna
Lebanon, Beirut
American University of Beirut
Nicot, Christophe
United States, Kansas City
University of Kansas Medical Center
United States, Westwood
University of Kansas Cancer Center
Hermine, Olivier
France, Paris
Hôpital Necker Enfants Malades
Hall, William W.
Ireland, Dublin
University College Dublin
de Thȩ, Hugues B.
France, Paris
Génomes, Biologie Cellulaire et Thérapeutique
Bazarbachi, Ali Abdul Hamid
Lebanon, Beirut
American University of Beirut
Statistics
Citations: 97
Authors: 15
Affiliations: 8
Identifiers
Doi:
10.1084/jem.20101095
ISSN:
00221007
e-ISSN:
15409538
Research Areas
Cancer