Adenovirus infection and cytotoxicity of primary mantle cell lymphoma cells.
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.
Medina
Daniel J
DJ
The Cancer Institute of New Jersey, Department of Medicine, Biomedical Center, Lund University, Lund, Sweden. medinadj@umdnj.edu
Sheay
Wendy
W
Osman
Mona
M
Goodell
Lauri
L
Martin
John
J
Rabson
Arnold B
AB
Strair
Roger K
RK
D000256:Adenoviridae / Q000235:genetics / Q000472:pathogenicity*; D000257:Adenoviridae Infections; D017500:Adenovirus E1A Proteins / Q000235:genetics; D017501:Adenovirus E1B Proteins / Q000172:deficiency / Q000235:genetics; D001691:Biological Therapy / Q000379:methods*; D016923:Cell Death; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000473:pathology / Q000628:therapy*; D009154:Mutation; D014613:Vaccines, Attenuated / Q000494:pharmacology; D014774:Virulence / Q000235:genetics
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D014613:Vaccines, Attenuated