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Chronic Lymphocytic Leukemia

Telomere length of cord blood-derived CD34+ progenitors predicts erythroid proliferative potential

Leukemia volume 21, pages 983–991 (2007)Cite this article

Abstract

Excessive telomere shortening has been demonstrated in inherited and acquired blood disorders, including aplastic anemia and myelodysplastic syndromes. It is possible that replicative exhaustion, owing to critical telomere shortening in hematopoietic progenitor cells (HPCs), contributes to the development of cytopenias in these disorders. However to date, a direct link between the telomere length (TL) of human HPCs and their proliferative potential has not been demonstrated. In the present investigation, the TL and level of telomerase enzyme activity (TA) detected in cord blood (CB)-derived HPCs was found to predict erythroid expansion (P<0.01 and P=0.01 respectively). These results were corroborated by a correlation between proliferation of erythroid cells and telomere loss (P=0.01). In contrast, no correlations were found between initial TL, telomere loss or TA and the expansion of other myeloid lineage-committed cells. There was also no correlation between TL or TA and the number of clonogenic progenitors, including primitive progenitors derived from long-term culture. Our investigations revealed upregulation of telomerase to tumor cell levels in CD34− cells undergoing erythroid differentiation. Together, these results provide new insight into the regulation of TL and TA during myeloid cell expansion and demonstrate that TL is an important determinant of CB-derived erythroid cell proliferation.

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Acknowledgements

We are grateful to the Australian Cord Blood Bank for providing umbilical cord blood and to Amgen for generous provision of cytokines. We thank Dr Leslie Ashton for statistical advice and Dr Richard Lock for reading this paper. Children's Cancer Institute Australia for Medical Research is affiliated with the University of New South Wales and Sydney Children's Hospital.

This work was funded by the Cancer Institute New South Wales and Cure Cancer Australia (formerly the Leo and Jenny Cancer and Leukaemia Foundation).

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  1. Stem Cell Biology Program, Children's Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia

    C E Schuller, K Jankowski & K L MacKenzie

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  1. C E Schuller
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Correspondence to K L MacKenzie.

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Schuller, C., Jankowski, K. & MacKenzie, K. Telomere length of cord blood-derived CD34+ progenitors predicts erythroid proliferative potential. Leukemia 21, 983–991 (2007). https://doi.org/10.1038/sj.leu.2404631

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