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 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.
Virgilio
L
L
Kimmel Cancer Institute and Department of Microbiology/Immunology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA. lvirgil@lac.jci.tju.edu
Lazzeri
C
C
Bichi
R
R
Nibu
K
K
Narducci
M G
MG
Russo
G
G
Rothstein
J L
JL
Croce
C M
CM
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*
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