This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sørensen, K. D.
Right arrow Articles by Pedersen, F. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sørensen, K. D.
Right arrow Articles by Pedersen, F. S.

 Previous Article  |  Next Article 

Journal of Virology, December 2004, p. 13216-13231, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13216-13231.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mutation of All Runx (AML1/Core) Sites in the Enhancer of T-Lymphomagenic SL3-3 Murine Leukemia Virus Unmasks a Significant Potential for Myeloid Leukemia Induction and Favors Enhancer Evolution toward Induction of Other Disease Patterns

Karina Dalsgaard Sørensen,1 Leticia Quintanilla-Martinez,2 Sandra Kunder,2 Jörg Schmidt,3 and Finn Skou Pedersen1,4*

Department of Molecular Biology,1 Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark,4 Institute of Pathology,2 Department of Comparative Medicine, GSF-National Research Center for Environment and Health, Neuherberg, Germany3

Received 4 May 2004/ Accepted 19 July 2004

SL3-3 murine leukemia virus is a potent inducer of T-lymphomas in mice. Using inbred NMRI mice, it was previously reported that a mutant of SL3-3 with all enhancer Runx (AML1/core) sites disrupted by 3-bp mutations (SL3-3dm) induces predominantly non-T-cell tumors with severely extended latency (S. Ethelberg, J. Lovmand, J. Schmidt, A. Luz, and F. S. Pedersen, J. Virol. 71:7273-7280, 1997). By use of three-color flow cytometry and molecular and histopathological analyses, we have now performed a detailed phenotypic characterization of SL3-3- and SL3-3dm-induced tumors in this mouse strain. All wild-type induced tumors had clonal T-cell receptor ß rearrangements, and the vast majority were CD3+ CD4+ CD8– T-lymphomas. Such a consistent phenotypic pattern is unusual for murine leukemia virus-induced T-lymphomas. The mutant virus induced malignancies of four distinct hematopoietic lineages: myeloid, T lymphoid, B lymphoid, and erythroid. The most common disease was myeloid leukemia with maturation. Thus, mutation of all Runx motifs in the enhancer of SL3-3 severely impedes viral T-lymphomagenicity and thereby discloses a considerable and formerly unappreciated potential of this virus for myeloid leukemia induction. Proviral enhancers with complex structural alterations (deletions, insertions, and/or duplications) were found in most SL3-3dm-induced T-lymphoid tumors and immature myeloid leukemias but not in any cases of myeloid leukemia with maturation, mature B-lymphoma, or erythroleukemia. Altogether, our results indicate that the SL3-3dm enhancer in itself promotes induction of myeloid leukemia with maturation but that structural changes may arise in vivo and redirect viral disease specificity to induction of T-lymphoid or immature myeloid leukemias, which typically develop with moderately shorter latencies.

* Corresponding author. Mailing address: Department of Molecular Biology, University of Aarhus, C. F. Møllers Allé, Bldg. 130, DK-8000 Aarhus C, Denmark. Phone: 45 8942 1111. Fax: 45 8619 6500. E-mail: fsp{at}mb.au.dk.

Journal of Virology, December 2004, p. 13216-13231, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13216-13231.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ejegod, D., Sorensen, K. D., Mossbrugger, I., Quintanilla-Martinez, L., Schmidt, J., Pedersen, F. S. (2009). Control of Pathogenicity and Disease Specificity of a T-Lymphomagenic Gammaretrovirus by E-Box Motifs but Not by an Overlapping Glucocorticoid Response Element. J. Virol. 83: 336-346 [Abstract] [Full Text]  
  • Kunder, S., Calzada-Wack, J., Holzlwimmer, G., Muller, J., Kloss, C., Howat, W., Schmidt, J., Hofler, H., Warren, M., Quintanilla-Martinez, L. (2007). A Comprehensive Antibody Panel for Immunohistochemical Analysis of Formalin-Fixed, Paraffin-Embedded Hematopoietic Neoplasms of Mice: Analysis of Mouse Specific and Human Antibodies Cross-Reactive with Murine Tissue. Toxicol Pathol 35: 366-375 [Abstract] [Full Text]  
  • Rodenburg, M., Fischer, M., Engelmann, A., Harbers, S. O., Ziegler, M., Lohler, J., Stocking, C. (2007). Importance of Receptor Usage, Fli1 Activation, and Mouse Strain for the Stem Cell Specificity of 10A1 Murine Leukemia Virus Leukemogenicity. J. Virol. 81: 732-742 [Abstract] [Full Text]  
  • Wang, C. L., Wang, B. B., Bartha, G., Li, L., Channa, N., Klinger, M., Killeen, N., Wabl, M. (2006). Activation of an oncogenic microRNA cistron by provirus integration. Proc. Natl. Acad. Sci. USA 103: 18680-18684 [Abstract] [Full Text]  
  • Dybkaer, K., Sorensen, K. D., Schmidt, J., d'Amore, F., Pedersen, F. S. (2005). Gene Expression Profiling Identifies Oncogenic Molecular Pathways in T-Lymphoma Induction by SL3-3 Retrovirus Insertional Mutagenesis in Inbred NMRI Mice.. ASH ANNUAL MEETING ABSTRACTS 106: 3010-3010 [Abstract]  
  • Glud, S. Z., Sorensen, A. B., Andrulis, M., Wang, B., Kondo, E., Jessen, R., Krenacs, L., Stelkovics, E., Wabl, M., Serfling, E., Palmetshofer, A., Pedersen, F. S. (2005). A tumor-suppressor function for NFATc3 in T-cell lymphomagenesis by murine leukemia virus. Blood 106: 3546-3552 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»