Dysregulated expression of the major telomerase components in leukaemic stem cells

Drummond, M.W., Hoare, S.F., Monaghan, A., Graham, S.M., Alcorn, M.J., Keith, W.N. and Holyoake, T.L. (2005) Dysregulated expression of the major telomerase components in leukaemic stem cells. Leukemia, 19(3), pp. 381-389. (doi:10.1038/sj.leu.2403616)

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Publisher's URL: http://dx.doi.org/10.1038/sj.leu.2403616

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hoare, Miss Stacey and Drummond, Dr Mark and Holyoake, Professor Tessa and Keith, Professor Nicol
Authors: Drummond, M.W., Hoare, S.F., Monaghan, A., Graham, S.M., Alcorn, M.J., Keith, W.N., and Holyoake, T.L.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Q Science > QH Natural history > QH426 Genetics
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Leukemia
ISSN:0887-6924

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