This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hays, E. F. Articles by Kronenberg, M. Search for Related Content PubMed PubMed Citation Articles by Hays, E. F. Articles by Kronenberg, M.

Development of Lymphoma in the Thymus of AKR Mice Treated with the Lymphomagenic Virus SL 3-3¹

Laboratory of Biomedical and Environmental Sciences [E. F. H.], Department of Medicine [E. F. H., G. C. B., S. M.] and The Jonsson Comprehensive Cancer Center [E. F. H., J. L. K., M. K.], University of California, Los Angeles, Los Angeles, California 90024

A chronological study of the individual thymic lobes of young AKR mice after neonatal inoculation of the oncogenic AKR retrovirus SL 3-3 was performed. 100% of mice treated in this manner develop lymphoma between 60 and 100 days of age. A search for early lymphoma cells in individual thymi was carried out by inoculating the thymocytes subcutaneously in syngeneic and intrathymically in syngeneic and semisyngeneic recipients. Tumor progression was observed in animals between 48 and 60 days of age. These animals have: (a) normal weight lobes, in which no lymphoma cells could be detected, (b) thymus-dependent lymphoma cells, in one or both normal weight lobes; (c) thymus-independent lymphoma cells, found in lobes of normal weight as well as in thymi enlarged by lymphoma cells. Thymocyte characteristics of virus-treated animals of 21 to 63 days of age were compared with those of age-matched controls. Beginning at 28 days a concordant, progressive with time, increase of thymocyte surface staining for the viral envelope glycoprotein gp70 was seen in all lobes from virus-treated animals. Evaluation of cell surface markers by two-color fluorescence with antibodies to CD4 and CD8 showed that after 50 days of age, thymic lobes with and without lymphomas had nonspecific, but marked, alterations of the typical thymocyte surface marker pattern. No characteristic CD4, CD8 surface phenotype was found in primary lymphomas.

Using probes for the T-cell receptor Jß2 gene segments and the Akv ecotropic virus gp70 envelope genes, oligoclonality in Jß2 rearrangements and clonality using the Akv env genes was demonstrated in thymi with the thymus-dependent phenotype. In lymphomas T-cell receptor ß gene probes showed either oligoclonality or clonality. Clonal virus integrations were found in these lymphomas.

These experiments suggest the following series of events in virusaccelerated AKR lymphomagenesis. First, lymphoma cells arise which are initially thymus-dependent and can appear in one or simultaneously in both thymic lobes. These progress to become thymus-independent, fully autonomous, tumor cells. Thymocytes close to or at the time of the initial transformation event show a marked disorder of differentiation defined by the alterations in the CD4, CD8 surface phenotype distribution.

¹ The Laboratory of Biomedical and Environmental Sciences is operated for the U. S. Department of Energy by the University of California under contract No. DE-FC03-87-ER60615. This manuscript was supported by the Director of the Office of Energy Research, Office of Health and Environmental Research, and by the National Institutes of Health, Grants CA12386 and CA45956.

² To whom requests for reprints should be addressed, at UCLA, Warren Hall, 900 Veteran Avenue, Los Angeles, CA 90024-1786.

Received 8/15/88. Revised 3/ 3/89. Accepted 5/ 4/89.

This article has been cited by other articles:

				S. Z. Glud, A. B. Sorensen, M. Andrulis, B. Wang, E. Kondo, R. Jessen, L. Krenacs, E. Stelkovics, M. Wabl, E. Serfling, et al. A tumor-suppressor function for NFATc3 in T-cell lymphomagenesis by murine leukemia virus Blood, November 15, 2005; 106(10): 3546 - 3552. [Abstract] [Full Text] [PDF]

				K. D. Sorensen, L. Quintanilla-Martinez, S. Kunder, J. Schmidt, and F. S. Pedersen 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 J. Virol., December 1, 2004; 78(23): 13216 - 13231. [Abstract] [Full Text] [PDF]

				K. Weinberg Can increased cytokine receptor signaling cause leukemia? Blood, March 15, 2004; 103(6): 1976 - 1977. [Full Text] [PDF]

				K. Rulli, J. Lenz, and L. S. Levy Disruption of Hematopoiesis and Thymopoiesis in the Early Premalignant Stages of Infection with SL3-3 Murine Leukemia Virus J. Virol., March 1, 2002; 76(5): 2363 - 2374. [Abstract] [Full Text] [PDF]

				F. K. Yoshimura, T. Wang, F. Yu, H.-R. C. Kim, and J. R. Turner Mink Cell Focus-Forming Murine Leukemia Virus Infection Induces Apoptosis of Thymic Lymphocytes J. Virol., September 1, 2000; 74(17): 8119 - 8126. [Abstract] [Full Text]

				F. K. Yoshimura, T. Wang, and M. Cankovic Sequences between the Enhancer and Promoter in the Long Terminal Repeat Affect Murine Leukemia Virus Pathogenicity and Replication in the Thymus J. Virol., June 1, 1999; 73(6): 4890 - 4898. [Abstract] [Full Text]

				C. H. Uittenbogaart, W. Law, P. J. M. Leenen, G. Bristol, W. van Ewijk, and E. F. Hays Thymic Dendritic Cells Are Primary Targets for the Oncogenic Virus SL3-3 J. Virol., December 1, 1998; 72(12): 10118 - 10125. [Abstract] [Full Text] [PDF]