Article (Scientific journals)
Valproate activates bovine leukemia virus gene expression, triggers apoptosis, and induces leukemia/lymphoma regression in vivo.
Achachi, Amine; Florins, Arnaud-Francois; Gillet, Nicolas et al.
2005In Proceedings of the National Academy of Sciences of the United States of America, 102 (29), p. 10309-14
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Keywords :
Animals; Apoptosis/drug effects; B-Lymphocytes/metabolism; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gene Expression Regulation, Viral/drug effects; Hela Cells; Histone Deacetylases/antagonists & inhibitors; Humans; Leukemia Virus, Bovine/metabolism; Leukemia, Lymphoid/therapy; Leukocytes, Mononuclear/metabolism; Luciferases; Lymphocyte Count; Proviruses/metabolism; Remission Induction; Sheep; Valproic Acid/pharmacology/therapeutic use
Abstract :
[en] Leukemogenic viruses like human T-lymphotropic virus and bovine leukemia virus (BLV) presumably persist in the host partly by latent integration of the provirus in a fraction of infected cells, leading to accumulative increase in the outgrowth of transformed cells. Furthermore, viral infection also correlates with a blockade of the apoptotic mechanisms concomitant with an apparent latency of the host cell. Conceptually, induction of viral or cellular gene expression could thus also be used as a therapeutic strategy against retroviral-associated leukemia. Here, we provide evidence that valproate, an inhibitor of deacetylases, activates BLV gene expression in transient transfection experiments and in short-term cultures of primary B-lymphocytes. In vivo, valproate injection into newly BLV-inoculated sheep did not abrogate primary infection. However, valproate treatment, in the absence of any other cytotoxic drug, was efficient for leukemia/lymphoma therapy in the sheep model leading to decreased lymphocyte numbers (respectively from 25.6, 35.7, and 46.5 x 10(3) cells per mm3 to 1.0, 10.6, and 24.3 x 10(3) cells per mm3 in three leukemic sheep) and tumor regression (from >700 cm3 to undetectable). The concept of a therapy that targets the expression of viral and cellular genes might be a promising treatment of adult T cell leukemia or tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy, diseases for which no satisfactory treatment exists so far.
Disciplines :
Oncology
Author, co-author :
Achachi, Amine 
Florins, Arnaud-Francois  ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Gillet, Nicolas  ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Debacq, Christophe
Urbain, Patrice
Foutsop, Germain Manfouo
Vandermeers, Fabian ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Jasik, Agnieszka
Reichert, Michal
Kerkhofs, Pierre
Lagneaux, Laurence
Burny, Arsène ;  Université de Liège - ULiège > Agro Biotech Gembloux
Kettmann, Richard ;  Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.
Willems, Luc  ;  Université de Liège - ULiège > GIGA-Research
More authors (4 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
Valproate activates bovine leukemia virus gene expression, triggers apoptosis, and induces leukemia/lymphoma regression in vivo.
Publication date :
2005
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
National Academy of Sciences, Washington, United States - District of Columbia
Volume :
102
Issue :
29
Pages :
10309-14
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 05 March 2011

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