Deregulated expression of TCL1 causes T cell leukemia in mice
AUTOR(ES)
Virgilio, Laura
FONTE
The National Academy of Sciences
RESUMO
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 p56lck promoter 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19932Documentos Relacionados
- Identification of the TCL1 gene involved in T-cell malignancies.
- Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression
- Chromosome walking on the TCL1 locus involved in T-cell neoplasia.
- TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues
- Dysregulated TCL1 promotes multiple classes of mature B cell lymphoma