Disruption of T-cell differentiation precedes T-cell tumor formation in LMO-2 (rhombotin-2) transgenic mice.
Transgenic mice expressing LMO-2 (rhombotin-2) were constructed by placing the LMO-2 gene under control of the metallothionein promoter. Thymic tumors developed in approximately 15% of the transgenic mice between 37 and 71 weeks. Only T-cell tumors were found in the transgenic mice despite high expression of LMO-2 in all tissues. The thymic tumors were aggressive and were invariably associated with metastasis to non-lymphoid organs. In approximately 50% of apparently healthy transgenic mice there was up to a 10-fold expansion of CD4-CD8- double negative (DN) cells. Expansion of the DN cells was accompanied by the compensatory decrease in CD4+CD8+ double positive (DP) cells, indicating that breach of homeostasis within the thymus had not occurred in these animals. The increase in DN cells was associated with a clonal expansion of thymocytes, and increased proliferation within the thymus. Our data indicate that the ectopic expression of LMO-2 in T-cells disrupts normal T-cell differentiation by selectively expanding the DN thymocyte population prior to breach of homeostasis and overt leukemia/lymphoma.
Neale
G A
GA
Department of Virology and Molecular Biology, St. Jude's Children's Research Hospital, Memphis, TN 38101, USA.
Rehg
J E
JE
Goorha
R M
RM
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D060588:LIM Domain Proteins; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000276:immunology; D008667:Metalloproteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011289:Preleukemia / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013953:Thymus Neoplasms / Q000235:genetics / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; C513188:Lmo2 protein, mouse; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins