Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Ectopic expression of proto-oncogene rhombotin-2 causes selective expansion of CD4-CD8- T-cell subset and thymic tumors in mice (Meeting abstract).
Proc Annu Meet Am Assoc Cancer Res; 36:A1125 1995. Unique Identifier : AIDSLINE ICDB/95608902 Goorha R; Neale G; Dept. of Virology and Molecular Biology, St. Jude Children's; Research Hosp., Memphis, TN 38101
Abstract:
The rhombotin-2 (RBTN-2) locus at chr 11p13 is the most frequent site of chromosomal translocation in childhood T-cell acute lymphoblastic leukemia. Although expressed widely, Rhom-2 is not expressed in T-lymphocytes. To investigate its mechanism of action in leukemogenesis, we constructed transgenic mice that express RBTN-2 in all tissues, including T-cells. Despite high expression of RBTN-2 in other tissues, these mice developed thymic tumors only, confirming RBTN-2 as a proto-oncogene specific for T-cells. Immunophenotype analysis, prior to tumor development, showed that the total number of thymocytes was similar but the proportion of CD4-CD8- lymphocytes was greatly increased in the thymus of transgenic mice (range 15-86%) compared with control mice (range 3-7%). T-cell receptor beta-chain gene analysis showed that in several pre-leukemic mice the thymocyte population represented monoclonal expansion. Presumably proliferating CD4-CD8- clones retain the capability to differentiate into CD4+CD8+ and mature single positive (CD3+CD4+ or CD3+CD8+) T-cells. Our results suggest that RBTN-2 causes selective proliferation of CD4-CD8- T-cells thereby creating a pool of T-cells, some of which may acquire subsequent changes required for tumorigenesis.
Keywords: Animal Cell Division CD4-CD8 Ratio DNA-Binding Proteins/*GENETICS/IMMUNOLOGY Leukemia, T-Cell/*GENETICS/IMMUNOLOGY/PATHOLOGY Metalloproteins/*GENETICS/IMMUNOLOGY Mice Mice, Transgenic T-Lymphocytes/CYTOLOGY/METABOLISM ABSTRACT 950930
M9591329
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