title: Deregulated expression of TCL1 causes T cell leukemia in mice.
abstract: 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 alpha or beta 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 p56(lck) 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.
authors.affiliation: Kimmel Cancer Institute and Department of Microbiology/Immunology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA. lvirgil@lac.jci.tju.edu
authors.forename: L
authors.initials: L
authors.lastname: Virgilio
authors.forename: C
authors.initials: C
authors.lastname: Lazzeri
authors.forename: R
authors.initials: R
authors.lastname: Bichi
authors.forename: K
authors.initials: K
authors.lastname: Nibu
authors.forename: M G
authors.initials: MG
authors.lastname: Narducci
authors.forename: G
authors.initials: G
authors.lastname: Russo
authors.forename: J L
authors.initials: JL
authors.lastname: Rothstein
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007942:Leukemia, Experimental / Q000235:genetics*; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; C490393:Tcl1 protein, mouse; D014157:Transcription Factors