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CML

Dysregulated expression of the major telomerase components in leukaemic stem cells

Leukemia volume 19, pages 381–389 (2005)Cite this article

Abstract

Telomere loss is rapid during the progression of chronic myeloid leukaemia (CML) and correlates with prognosis. We therefore sought to measure expression of the major telomerase components (hTR and hTERT) in CD34+ cells from CML patients and normal controls, to determine if their altered expression may contribute to telomere attrition in vivo. High-purity (median 94.1%) BCR-ABL+ CD34+ cells from CML (n=16) and non-CML (n=14) patients were used. CML samples had a small increase in telomerase activity (TA) compared to normal samples (approximately 1.5-fold, P=0.004), which was inversely correlated with the percentage of G0 cells (P=0.02) suggesting TA may not be elevated on a cell-to-cell basis in CML. Consistent with this, hTERT mRNA expression was not significantly elevated; however, altered mRNA splicing appeared to play a significant role in determining overall full length, functional hTERT levels. Interestingly, Q-RT-PCR for hTR demonstrated a mean five-fold reduction in levels in the chronic phase (CP) CML samples (P=0.002), raising the possibility that telomere homeostasis is disrupted in CML. In summary, the molecular events regulating telomerase gene expression and telomere maintenance during the CP of CML may influence the disease progression observed in these patients.

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Acknowledgements

We thank Junia Melo (Hammersmith Hospital, London, UK) for kindly providing many of the leukaemia cell lines used in these experiments, and Steve O'Brien and Anne Lennard (Royal Victoria Hospital, Newcastle-upon-Tyne, UK), Richard Clark (Royal Liverpool Hospital) and John Goldman (Hammersmith Hospital, London, UK) for providing leucapheresis material. This work was supported by the Leukaemia Research Fund (Grant Numbers 99/65 and 02/39). This work was supported by the Leukaemia Research Fund, UK (LRF Grant Numbers 99/65 and 02/39) and the University of Glasgow. S Hoare, A Monaghan and WN Keith are supported by Cancer Research UK and University of Glasgow. S Graham is supported by the Chief Scientist's Office.

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Authors and Affiliations

  1. Section of Experimental Haematology, Division of Cancer Sciences and Molecular Pathology, University of Glasgow, 10 Alexandra Parade, Glasgow, UK

    M W Drummond, S M Graham & T L Holyoake

  2. Cancer Research UK Department of Medical Oncology, University of Glasgow, Beatson Laboratories, Garscube Estate, Switchback Rd, Glasgow, UK

    S F Hoare, A Monaghan & W N Keith

  3. Department of Haematology, Glasgow Royal Infirmary, Castle Street, Glasgow, UK

    M J Alcorn

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  1. M W Drummond
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Correspondence to M W Drummond.

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Drummond, M., Hoare, S., Monaghan, A. et al. Dysregulated expression of the major telomerase components in leukaemic stem cells. Leukemia 19, 381–389 (2005). https://doi.org/10.1038/sj.leu.2403616

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