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Apoptosis

Human telomerase reverse transcriptase protects hematopoietic progenitor TF-1 cells from death and quiescence induced by cytokine withdrawal

Leukemia volume 20, pages 1270–1278 (2006)Cite this article

Abstract

Telomerase is a complex ribonucleoprotein enzyme that exhibits elevated activity in the majority of cases of human leukemia. We have previously shown that retroviral expression of the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), in human cord blood CD34+ cells leads to an enhanced survival of mature hematopoietic cells. The mechanism for this pro-survival effect is not known. Here, we show that telomerase may play a role in leukemogenesis as a survival factor, independent of its role in maintaining telomere length. Retroviral expression of hTERT in the cytokine-dependent, human hematopoietic progenitor cell line, TF-1, resulted in the survival of cells following the withdrawal of cytokine, with protection from apoptosis, but did not promote unlimited replicative potential. This hTERT-mediated effect on cell survival does not involve Bcl-2 family members, results in accumulation of cells in G1 and appears to operate via autocrine expression of IL-3 and activation of the p53/p21 pathway. Survival in the absence of cytokine stimulation was also observed following retroviral expression of hTERT in normal cord blood CD34+ cells. This study demonstrates a novel pro-survival role for hTERT and may have important implications for the role of hTERT in the pathogenesis of leukemia and drug resistance.

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Acknowledgements

We thank the BMDI Cord Blood Bank for supply of human cord blood for research purposes. This work was supported by the Leukemia Research Fund of the Royal Children's Hospital, the Leukaemia Auxiliary of the Royal Children's Hospital, the Murdoch Children's Research Institute and a University of Melbourne Early Career Grant.

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  1. Murdoch Children's Research Institute and Department of Paediatrics, Children's Cancer Centre, Royal Children's Hospital, University of Melbourne, Parkville, Victoria, Australia

    S Li, M J Ferguson, C J Hawkins & N J Elwood

  2. Leukemia/BMT Program of British Columbia, Vancouver, Canada

    C Smith

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  1. S Li
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  2. M J Ferguson
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  3. C J Hawkins
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  4. C Smith
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Correspondence to N J Elwood.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Li, S., Ferguson, M., Hawkins, C. et al. Human telomerase reverse transcriptase protects hematopoietic progenitor TF-1 cells from death and quiescence induced by cytokine withdrawal. Leukemia 20, 1270–1278 (2006). https://doi.org/10.1038/sj.leu.2404251

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