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Chronic Lymphocytic Leukemia

Short telomeres and high telomerase activity in T-cell prolymphocytic leukemia

Leukemia volume 21, pages 2456–2462 (2007)Cite this article

Abstract

To test the role of telomere biology in T-cell prolymphocytic leukemia (T-PLL), a rare aggressive disease characterized by the expansion of a T-cell clone derived from immuno-competent post-thymic T-lymphocytes, we analyzed telomere length and telomerase activity in subsets of peripheral blood leukocytes from 11 newly diagnosed or relapsed patients with sporadic T-PLL. Telomere length values of the leukemic T cells (mean±s.d.: 1.53±0.65 kb) were all below the 1st percentile of telomere length values observed in T cells from healthy age-matched controls whereas telomere length of normal T- and B cells fell between the 1st and 99th percentile of the normal distribution. Leukemic T cells exhibited high levels of telomerase and were sensitive to the telomerase inhibitor BIBR1532 at doses that showed no effect on normal, unstimulated T cells. Targeting the short telomeres and telomerase activity in T-PLL seems an attractive strategy for the future treatment of this devastating disease.

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Acknowledgements

This paper is dedicated to Professor Günter Brittinger on the occasion of his 75th birthday. We thank Anja Führer and Margret Gottlieb for their expert technical assistance. We are grateful to Boehringer Ingelheim Pharma KG (Biberach, Germany) for providing us with BIBR1532. We thank Dr Lana Harder for her help with cytogenetic analyses, Dr Nückel for helping with statistical analysis and Dr Ludger Klein-Hitpass (Institute for Cell Biology, Essen, Germany) for his help with hTERT RT-PCR. This work was supported by a grant from the Bernese Cancer League (to GMB).

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Authors and Affiliations

  1. Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    A Röth, J Dürig & U Dührsen

  2. Department of Hematology, University Hospital, Bern, Switzerland

    H Himmelreich & G M Baerlocher

  3. Department of Clinical Research, University Hospital, Bern, Switzerland

    H Himmelreich & G M Baerlocher

  4. Institute of Human Genetics, Christian-Albrechts-University Hospital Schleswig-Holstein, Kiel, Germany

    S Bug & R Siebert

  5. Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, Canada

    P M Lansdorp

  6. Department of Medicine, University of British Columbia, Vancouver, Canada

    P M Lansdorp

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  1. A Röth
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  6. U Dührsen
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  7. P M Lansdorp
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  8. G M Baerlocher
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Corresponding authors

Correspondence to A Röth or G M Baerlocher.

Additional information

Contributions: AR, JD and GMB designed the research; AR, HH, SB and GMB performed the experiments and collected the data; AR, JD, RS and GMB analyzed and interpreted the data; AR, RS, UD, PML and GMB wrote the paper.

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Röth, A., Dürig, J., Himmelreich, H. et al. Short telomeres and high telomerase activity in T-cell prolymphocytic leukemia. Leukemia 21, 2456–2462 (2007). https://doi.org/10.1038/sj.leu.2404968

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