Deregulated Expression of TCL1 Causes T Cell Leukemia in Mice

The TCL1 oncogene on human chromosome 14q32.1 is involved in the development of T cell leukemia in humans. These leukemias are classified either as T prolymphocytic leukemias, which occur very late in life, or as T chronic lymphocytic leukemias, which often arise in patients with ataxia telangiectas...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-03, Vol.95 (7), p.3885-3889
Main Authors: Virgilio, Laura, Lazzeri, Cristina, Bichi, Roberta, Nibu, Ken-Ichi, Narducci, Maria Grazia, Russo, Giandomenico, Rothstein, Jay L., Croce, Carlo M.
Format: Article
Language:English
Subjects:
Animals
Antibodies
Biological Sciences
CD4 Antigens - immunology
CD8 Antigens - immunology
Cells
Developmental biology
DNA
DNA-Binding Proteins - genetics
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Leukemia
Leukemia, Experimental - genetics
Leukemia, T-Cell - genetics
Leukemia, T-Cell - immunology
Lymphocytes
Medical research
Mice
Mice, Transgenic
Proto-Oncogene Proteins
Rodents
Spleen
T cell leukemia
T lymphocytes
T-Lymphocyte Subsets - immunology
Transcription Factors - genetics
Transgenic animals
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Summary:The TCL1 oncogene on human chromosome 14q32.1 is involved in the development of T cell leukemia in humans. These leukemias are classified either as T prolymphocytic leukemias, which occur very late in life, or as T chronic lymphocytic leukemias, which often arise in patients with ataxia telangiectasia (AT) at a young age. The TCL1 oncogene is activated in these leukemias by juxtaposition to the α or β locus of the T cell receptor, caused by chromosomal translocations t(14:14)(q11:q32), t(7:14)(q35:q32), or by inversions inv(14)(q11:q32). To show that transcriptional alteration of TCL1 is causally involved in the generation of T cell neoplasia we have generated transgenic mice that carry the TCL1 gene under the transcriptional control of the p56lckpromoter element. The lck-TCL1 transgenic mice developed mature T cell leukemias after a long latency period. Younger mice presented preleukemic T cell expansions expressing TCL1, and leukemias developed only at an older age. The phenotype of the murine leukemias is CD4-CD8+, in contrast to human leukemias, which are predominantly CD4+CD8-. These studies demonstrate that transcriptional activation of the TCL1 protooncogene can cause malignant transformation of T lymphocytes, indicating the role of TCL1 in the initiation of malignant transformation in T prolymphocytic leukemias and T chronic lymphocytic leukemias.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.7.3885