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Telomeres and prognosis in patients with chronic lymphocytic leukaemia

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Abstract

In the present study, telomere length, telomerase activity, the mutation load of immunoglobulin variable heavy chain (IGHV) genes, and established prognostic factors were investigated in 78 patients with chronic lymphocytic leukaemia (CLL) to determine the impact of telomere biology on the pathogenesis of CLL. Telomere length was measured by an automated multi-colour flow-FISH, and an age-independent delta telomere length (ΔTL) was calculated. CLL with unmutated IGHV genes was associated with shorter telomeres (p = 0.002). Furthermore, we observed a linear correlation between the frequency of IGHV gene mutations and elongation of telomeres (r = 0.509, p < 0.001). With respect to prognosis, a threshold ΔTL of −4.2 kb was the best predictor for progression-free and overall survival. ΔTL was not significantly altered over time or with therapy. The correlation between the mutational load in IGHV genes and the ΔTL in CLL might reflect the initial telomere length of the putative cell of origin (pre- versus post-germinal center B cells). In conclusion, the ΔTL is a reliable prognostic marker for patients with CLL. Short telomeres and high telomerase activity as occurs in some patients with CLL with a worse prognosis might be an ideal target for treatment with telomerase inhibitors.

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Acknowledgments

We thank Anja Führer, Songül Basoglu, Barbara Friedmann, Andrea Kopplin, and Ute Schmücker for their expert technical assistance. This work was supported by a grant from the Bernese Cancer League (G.M.B.) and from the IFORES program of the University Duisburg Essen (L.S.).

Conflict of interest

The other authors declare no competing financial interests.

Author information

Authors and Affiliations

  1. Department of Haematology, University of Duisburg Essen, Essen, Germany

    Ludger Sellmann, Marius Bartels, Bertram Opalka, Holger Nückel, Ulrich Dührsen, Jan Dürig & Alexander Röth

  2. Institute of Cell Biology (Cancer Research), University of Duisburg Essen, Essen, Germany

    Ludger Sellmann, Marc Seifert, Dörte Siemer & Ralf Küppers

  3. Experimental Haematology, Department of Clinical Research, University of Bern, Bern, Switzerland

    Dirk de Beer & Gabriela M. Baerlocher

  4. Department of Haematology, University Hospital Bern, Bern, Switzerland

    Gabriela M. Baerlocher

  5. Department of Haematology, University Hospital, Hufelandstrasse 55, 45122, Essen, Germany

    Ludger Sellmann

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  1. Ludger Sellmann
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Corresponding author

Correspondence to Ludger Sellmann.

Additional information

G. M. Baerlocher and A. Röth contributed equally.

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Sellmann, L., de Beer, D., Bartels, M. et al. Telomeres and prognosis in patients with chronic lymphocytic leukaemia. Int J Hematol 93, 74–82 (2011). https://doi.org/10.1007/s12185-010-0750-2

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  • DOI: https://doi.org/10.1007/s12185-010-0750-2

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