Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Chronic Lymphocytic Leukemia

TCL1 shows a regulated expression pattern in chronic lymphocytic leukemia that correlates with molecular subtypes and proliferative state

Leukemia volume 20, pages 280–285 (2006)Cite this article

Abstract

Expression of the human oncogene TCL1 in transgenic mice produces B-cell tumors that resemble chronic lymphocytic leukemia (CLL) suggesting its role in B-cell tumorigenesis. To clarify the expression pattern and regulation of TCL1 in CLL, we assessed 213 primary tumors by immunohistochemistry (IHC), flow-cytometry and/or Western blot, using a new monoclonal antibody. TCL1 protein was detectable in the majority of CLL (90% by IHC) but showed marked variations across cases with virtual absence in approximately 10% of tumors. Higher TCL1 levels correlated with markers of the ‘pre-germinal center’ CLL subtype including unmutated VH status (P=0.005), ZAP70 expression (P=0.007), and presence of chromosome 11q22–23 deletions (P=0.04). Intratumoral heterogeneity in TCL1 levels was also prominent and explained in part by markedly lower TCL1 expression in proliferating tumor cells. In vitro exposure of CLL cells to interleukin-4 (but not other growth factors) produced progressive and irreversible decrease in TCL1 protein levels in association with the onset of proliferation. TCL1 expression patterns in CLL are complex and highly dynamic and appear to reflect both the histogenetic subtypes of the disease and the growth parameters of individual tumors. The observed regulation pattern suggests that TCL1 may exert its effects predominantly in the unmutated/ZAP70-positive tumor subset.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Brito-Babapulle V, Catovsky D . Inversions and tandem translocations involving chromosome 14q11 and 14q32 in T-prolymphocytic leukemia and T-cell leukemias in patients with ataxia telangiectasia. Cancer Genet Cytogenet 1991; 55: 1–9.

    Article  CAS  Google Scholar 

  2. Virgilio L, Isobe M, Narducci MG, Carotenuto P, Camerini B, Kurosawa N et al. Chromosome walking on the TCL1 locus involved in T-cell neoplasia. Proc Natl Acad Sci USA 1993; 90: 9275–9279.

    Article  CAS  Google Scholar 

  3. Virgilio L, Narducci MG, Isobe M, Billips LG, Cooper MD, Croce CM et al. Identification of the TCL1 gene involved in T-cell malignancies. Proc Natl Acad Sci USA 1994; 91: 12530–12534.

    Article  CAS  Google Scholar 

  4. Isobe M, Russo G, Haluska FG, Croce CM . Cloning of the gene encoding the delta subunit of the human T-cell receptor reveals its physical organization within the alpha-subunit locus and its involvement in chromosome translocations in T-cell malignancy. Proc Natl Acad Sci USA 1988; 11: 3933–3937.

    Article  Google Scholar 

  5. Russo G, Isobe M, Gatti R, Finan J, Batuman O, Huebner K et al. Molecular analysis of a t(14;14) translocation in leukemic T-cells of an ataxia telangiectasia patient. Proc Natl Acad Sci USA 1989; 86: 602–606.

    Article  CAS  Google Scholar 

  6. Virgilio L, Lazzeri C, Bichi R, Nibu K, Narducci MG, Russo G et al. Deregulated expression of TCL1 causes T cell leukemia in mice. Proc Natl Acad Sci USA 1998; 95: 3885–3889.

    Article  CAS  Google Scholar 

  7. Matutes E, Brito-Babapulle V, Swansbury J, Ellis J, Morilla R, Dearden C et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood 1991; 78: 3269–3274.

    CAS  PubMed  Google Scholar 

  8. Soulier J, Pierron G, Vecchione D, Garand R, Brizard F, Sigaux F et al. A complex pattern of recurrent chromosomal losses and gains in T-cell prolymphocytic leukemia. Genes Chromosomes Cancer 2001; 31: 248–254.

    Article  CAS  Google Scholar 

  9. Herling M, Khoury JD, Washington LT, Duvic M, Keating MJ, Jones D . A systematic approach to diagnosis of mature T-cell leukemias reveals heterogeneity among WHO categories. Blood 2004; 104: 328–335.

    Article  CAS  Google Scholar 

  10. Narducci MG, Fiorenza MT, Kang SM, Bevilacqua A, Di Giacomo M, Remotti D et al. TCL1 participates in early embryonic development and is overexpressed in human seminomas. Proc Natl Acad Sci USA 2002; 99: 11712–11717.

    Article  CAS  Google Scholar 

  11. Herling M, Teitell MA, Shen RR, Medeiros LJ, Jones D . TCL1 expression in plasmacytoid dendritic cells (DC2s) and the related CD4+ CD56+ blastic tumors of skin. Blood 2003; 101: 5007–5009.

    Article  CAS  Google Scholar 

  12. Hoyer KK, Herling M, Bagrintseva K, Dawson DW, French SW, Renard M et al. T cell leukemia-1 modulates TCR signal strength and IFN-{gamma} levels through phosphatidylinositol 3-kinase and protein kinase C pathway activation. J Immunol 2005; 175: 864–873.

    Article  CAS  Google Scholar 

  13. Narducci MG, Pescarmona E, Lazzeri C, Signoretti S, Lavinia AM, Remotti D et al. Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues. Cancer Res 2000; 60: 2095–2100.

    CAS  PubMed  Google Scholar 

  14. Nakayama I, Murao S, Kitazawa S, Azumi A, Yamamoto M, Maeda S . Activation of the TCL1 protein in B cell lymphomas. Pathol Int 2000; 50: 191–199.

    Article  CAS  Google Scholar 

  15. Said JW, Hoyer KK, French SW, Rosenfelt L, Garcia-Lloret M, Koh PJ et al. TCL1 oncogene expression in B cell subsets from lymphoid hyperplasia and distinct classes of B cell lymphoma. Lab Invest 2001; 81: 555–564.

    Article  CAS  Google Scholar 

  16. Roos J, Hennig I, Schwaller J, Zbaren J, Dummer R, Burg G et al. Expression of TCL1 in hematologic disorders. Pathobiology 2001; 69: 59–66.

    Article  CAS  Google Scholar 

  17. Teitell M, Damore MA, Sulur GG, Turner DE, Stern MH, Said JW et al. TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues. Proc Natl Acad Sci USA 1999; 96: 9809–9814.

    Article  CAS  Google Scholar 

  18. Fink SR, Paternoster SF, Smoley SA, Flynn HC, Geyer SM, Shanafelt TD et al. Fluorescent-labeled DNA probes applied to novel biological aspects of B-cell chronic lymphocytic leukemia. Leuk Res 2005; 29: 253–262.

    Article  CAS  Google Scholar 

  19. Bichi R, Shinton SA, Martin ES, Koval A, Calin GA, Cesari R et al. Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression. Proc Natl Acad Sci USA 2002; 99: 6955–6960.

    Article  CAS  Google Scholar 

  20. Hoyer KK, French SW, Turner DE, Nguyen MT, Renard M, Malone CS et al. Dysregulated TCL1 promotes multiple classes of mature B cell lymphoma. Proc Natl Acad Sci USA 2002; 99: 14392–14397.

    Article  CAS  Google Scholar 

  21. Ottensmeier CH, Thompsett AR, Zhu D, Wilkins BS, Sweetenham JW, Stevenson FK . Analysis of VH genes in follicular and diffuse lymphoma shows ongoing somatic mutation and multiple isotype transcripts in early disease with changes during disease progression. Blood 1998; 91: 4292–4299.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a NCI Grant CA16672 and an Odyssey Fellowship (to MH).

Author information

Authors and Affiliations

  1. Department of Hematopathology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA

    M Herling, K A Patel, J Khalili, E Schlette, L J Medeiros & D Jones

  2. Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    R Kobayashi

Authors
  1. M Herling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K A Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Khalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Schlette
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L J Medeiros
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Jones.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herling, M., Patel, K., Khalili, J. et al. TCL1 shows a regulated expression pattern in chronic lymphocytic leukemia that correlates with molecular subtypes and proliferative state. Leukemia 20, 280–285 (2006). https://doi.org/10.1038/sj.leu.2404017

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404017

Keywords

Search

Advanced search

Quick links