Deregulated expression of TCL1 causes T cell leukemia in mice

Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3885-9. doi: 10.1073/pnas.95.7.3885.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4 Antigens / immunology
  • CD8 Antigens / immunology
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Leukemia, Experimental / genetics*
  • Leukemia, T-Cell / genetics*
  • Leukemia, T-Cell / immunology
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins*
  • T-Lymphocyte Subsets / immunology
  • Transcription Factors / genetics*


  • CD4 Antigens
  • CD8 Antigens
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • TCL1A protein, human
  • Tcl1 protein, mouse
  • Transcription Factors