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Chronic Myeloid Leukemia, BCR/ABL Studies and Myeloproliferative Disorders

hTERT, the catalytic component of telomerase, is downregulated in the haematopoietic stem cells of patients with chronic myeloid leukaemia

Leukemia volume 20, pages 671–679 (2006)Cite this article

Abstract

Telomere shortening is associated with disease progression in chronic myeloid leukaemia (CML). To investigate the biology and regulation of telomerase in CML, we evaluated expression of the telomerase components, its regulators and several telomeric-associated proteins. Quantitative real-time-polymerase chain reaction (PCR) was used to compare gene expression in the CD34+/leukaemic blast cells of 22 CML patient samples to the CD34+ cell population of healthy individuals. hTERT, the catalytic component of telomerase, was downregulated in eight of 12 chronic phase (CP) patients (P=0.0387). Furthermore, hTERT was significantly downregulated in two of three patients in accelerated phase (AP) and seven of seven patients in blast crisis (BC), P=0.0017. Expression of hTR and telomeric-associated proteins TEP1, TRF1, TRF2, tankyrase and PinX1 was high in the majority of CP and AP patients. With the exceptions of TEP1 and hTR, expression of these factors was highest in CP and decreased during disease progression. Expression of c-Myc, a positive regulator of hTERT transcription, correlated with hTERT expression and decreased with disease progression, falling below control levels in BC. hTERT levels were increased in CP patients following successful treatment with imatinib, relative to untreated CP patients. We suggest that reduced hTERT expression directly causes the shortened telomeres observed in CML.

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Acknowledgements

This work was supported by grants from the Kay Kendall Leukaemia Fund and the Leukaemia Research Fund.

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  1. Nuffield Department of Clinical Laboratory Sciences, Leukaemia Research Fund Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK

    L J Campbell, C Fidler, H Eagleton, A Peniket, S Gal, T J Littlewood, J S Wainscoat & J Boultwood

  2. Department of Clinical Sciences, Department of Haematology, University Hospital Merkur, Zagreb, Croatia

    R Kusec

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  1. L J Campbell
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Campbell, L., Fidler, C., Eagleton, H. et al. hTERT, the catalytic component of telomerase, is downregulated in the haematopoietic stem cells of patients with chronic myeloid leukaemia. Leukemia 20, 671–679 (2006). https://doi.org/10.1038/sj.leu.2404141

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