Deregulated expression of TCL1 causes T cell leukemia in mice

Laura Virgilio, Cristina Lazzeri, Roberta Bichi, Ken Ichi Nibu, Maria Grazia Narducci, Giandomenico Russo, Jay L. Rothstein, Carlo M. Croce

Research output: Contribution to journalArticlepeer-review

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 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 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 oft lymphocytes, indicating the role of TCL1 in the initiation of malignant transformation in T prolymphocytic leukemias and T chronic lymphocytic leukemias.

Original languageEnglish
Pages (from-to)3885-3889
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number7
DOIs
Publication statusPublished - Mar 31 1998

ASJC Scopus subject areas

  • Genetics
  • General

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