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Adenovirus infection and cytotoxicity of primary mantle cell lymphoma cells

Authors :
Medina, Daniel J.
Sheay, Wendy
Osman, Mona
Goodell, Lauri
Martin, John
Rabson, Arnold B.
Strair, Roger K.
Source :
Experimental Hematology. Nov2005, Vol. 33 Issue 11, p1337-1347. 11p.
Publication Year :
2005

Abstract

Mantle cell lymphoma (MCL) is a distinct form of non-Hodgkin''s lymphoma (NHL) derived from CD5+ B cells. MCL cells overexpress cyclin D1 as a consequence of translocation of the gene into the immunoglobulin heavy-chain gene locus. MCL is an aggressive form of NHL with frequent relapses after standard-dose chemotherapy. In this context, a variety of novel therapies for patients with MCL have been investigated. In this study, we use an expanded panel of attenuated adenoviruses to study adenovirus-mediated cytotoxicity of MCL cells. Our results demonstrate: 1) adenovirus infection of MCL cells despite the absence of receptor/coreceptor molecules known to be important for adenovirus infection of other cells types; 2) cytotoxicity of MCL cells after infection with specific adenovirus mutants; 3) a high degree of cytotoxicity after infection of some patient samples with viruses lacking the E1B 19k “antiapoptotic” gene; and 4) cytotoxicity after infection with viruses containing mutations in E1A pRb or p300 binding. The extent of cytotoxicity with the panel of viruses demonstrated interpatient variability, but 100% cytotoxicity, as determined by molecular analysis, was detected in some samples. These studies provide the foundation for: 1) the development of adenoviruses as cytotoxic agents for MCL and 2) analyses of key regulatory pathways operative in MCL cells. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
0301472X
Volume :
33
Issue :
11
Database :
Academic Search Index
Journal :
Experimental Hematology
Publication Type :
Academic Journal
Accession number :
18983655
Full Text :
https://doi.org/10.1016/j.exphem.2005.07.009