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Aberrant telomere structure is characteristic of resistant chronic lymphocytic leukaemia cells

Leukemia volume 24, pages 246–251 (2010)Cite this article

Telomeres are the capping structures of chromosome ends and are composed of repeated DNA sequences (∼10 kb in adult somatic cells) and a specific set of associated proteins. The regulation of telomere length results from the action of telomere-lengthening mechanisms, such as the telomerase complex (hTERT, hTR and dyskerin), and of telomere-shortening mechanisms, such as replication and recombination. Telomerase activity is regulated in cis by the shelterin hexa–protein complex (TRF1, TRF2, hRAP1, POT1, TIN2 and TPP1) and epigenetic factors.1, 2 Proteins involved in DNA replication and repair are also associated in telomeric structure and function.2 The shortening of telomere sequences upon cell divisions in most somatic cells results in irreversible cell growth arrest called senescence or in apoptosis. A change in telomere function is one of the main mechanisms underlying the evolution and maintenance of cancer cells. Telomere erosion may be critical in tumour suppression as it impairs cell proliferation. In many cancer cells, this is circumvented by reactivating the expression and/or activity of telomerase or by homologous recombination.1, 2

Chronic lymphocytic leukaemia (CLL) is a B-cell malignancy with increased incidence among the elderly. The disease is due to an imbalance between cell death and proliferation resulting in an accumulation of malignant cells in the bone marrow and peripheral blood (reviewed in Van Bockstaele et al.3). Clinically, the disease varies from indolent, which may progress to/or appear at diagnostic as an aggressive incurable form. The most commonly used biological markers for the disease outcome are the type of chromosomal aberration and the mutational status of immunoglobulin heavy-chain variable region genes (IgVH), often associated with the expression status of Zap70 tyrosine kinase (reviewed in Van Bockstaele et al.3). The telomere length and telomerase activity are further prognostic markers as unfavourable disease was associated with short telomeres4 (reviewed in Van Bockstaele et al.3). This, together with altered expression of several telomeric components,5 indicates that telomeres are profoundly rearranged in CLL cells.

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Acknowledgements

We are grateful to all leukaemic donors who have signed informed consent form. This work was supported by ARC (ARECA project). Approval for this study was obtained from the institutional review boards of the CEA and the Pitié-Salpêtrière Hospital.

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Authors and Affiliations

  1. Laboratoire d'Onco-Hématologie, iRCM, DSV, Commissariat à l'Energie Atomique (CEA), Fontenay aux Roses, France

    T Brugat, N Gault, I Baccelli & J Delic

  2. Institut Universitaire d'Hématologie, Université Paris 7, Paris, France

    J Maës & M Goodhardt

  3. INSERM U662, Paris, France

    J Maës & M Goodhardt

  4. Laboratoire de Biologie Moléculaire et de Cellule, CNRS UMR5239, Faculté de Médecine Lyon Sud, Université Lyon 1, Lyon, France

    A Roborel de Climens & E Gilson

  5. Service d'Hématologie Biologique, Hôpital Pitié-Salpêtrière and Université Paris 6, Paris, France

    F Nguyen-Khac, F Davi & H Merle-Béral

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  1. T Brugat
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Brugat, T., Gault, N., Baccelli, I. et al. Aberrant telomere structure is characteristic of resistant chronic lymphocytic leukaemia cells. Leukemia 24, 246–251 (2010). https://doi.org/10.1038/leu.2009.213

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