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Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression.

The TCL1 gene at 14q32.1 is involved in chromosomal translocations and inversions in mature T cell leukemias. 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. In transgenic animals, the deregulated expression of TCL1 leads to mature T cell leukemia, demonstrating the role of TCL1 in the initiation of malignant transformation in T cell neoplasia. Expression of high levels of Tcl1 have also been found in a variety of human tumor-derived B cell lines ranging from pre-B cell to mature B cell. Here we describe the phenotype of transgenic mice, E mu-TCL1, established with TCL1 under the control of a V(H) promoter-Ig(H)-E mu enhancer to target TCL1 expression to immature and mature B cells. Flow cytometric analysis reveals a markedly expanded CD5(+) population in the peritoneal cavity of E mu-TCL1 mice starting at 2 mo of age that becomes evident in the spleen by 3-5 mo and in the bone marrow by 5-8 mo. Analysis of Ig gene rearrangements indicates monoclonality or oligoclonality in these populations, suggesting a preneoplastic expansion of CD5(+) B cell clones, with the elder mice eventually developing a chronic lymphocytic leukemia (CLL)-like disorder resembling human B-CLL. Our findings provide an animal model for CLL, the most common human leukemia, and demonstrate that deregulation of the Tcl1 pathway plays a crucial role in CLL pathogenesis.

Pubmed ID: 12011454


  • Bichi R
  • Shinton SA
  • Martin ES
  • Koval A
  • Calin GA
  • Cesari R
  • Russo G
  • Hardy RR
  • Croce CM


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

May 14, 2002

Associated Grants


Mesh Terms

  • Aging
  • Animals
  • Antigens, CD5
  • Cell Cycle
  • DNA-Binding Proteins
  • Disease Models, Animal
  • G0 Phase
  • G1 Phase
  • Gene Targeting
  • Humans
  • Immunoenzyme Techniques
  • Immunoglobulin Heavy Chains
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • Immunophenotyping
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Mice
  • Mice, Transgenic
  • Plasmids
  • Proto-Oncogene Proteins
  • Transcription Factors