Mark W. Drummonda, Stefan Balabanovb, Tessa L. Holyoakec, Tim H. Brummendorfb
aDepartment of Haematology, Western Infirmary, Glasgow, United Kingdom;
bDepartment of Oncology and Hematology, University Medical Center Eppendorf, Hamburg, Germany;
cSection of Experimental Hematology, University of Glasgow, Glasgow, United Kingdom
Key Words. Telomere • Telomerase • Stem cell • Aging • Leukemia • Bone marrow failure
Correspondence: Mark W. Drummond, M.B., Ch.B., Ph.D., M.R.C.Path., Department of Haematology, Western Infirmary, Glasgow G11 6NT, U.K. Telephone: 0044-141-211-2156; Fax: 0044-141-211-6296; e-mail: [email protected]
Received January 22, 2007; accepted for publication April 9, 2007.
First published online in STEM CELLS EXPRESS May 17, 2007.
The measurement of telomere length can give an insight intothe replicative history of the cells in question. Much of theobserved telomere loss occurs at the stem and progenitor celllevel, even though these populations express the enzyme telomerase.Telomerase-transfected hematopoietic stem cells (HSC), althoughable to maintain telomere length, are still limited in termsof ability to undergo sequential transplantation, and otherfactors require to be addressed to achieve optimal levels ofstem cell expansion. Unchecked telomere loss by HSC, meanwhile,would appear to play a significant role in the pathogenesisof bone marrow failure, as observed in the condition dyskeratosiscongenita. This heterogeneous inherited condition appears toexhibit telomerase dysfunction as a common final pathogenicmechanism. Although less well-established for acquired marrowfailure syndromes, mutations in key telomerase components havebeen described. The identification of the leukemic stem cell(LSC), along with the desire to target this population withanti-leukemia therapy, demands that telomerase biology be fullyunderstood in this cell compartment. Future studies using primaryselected LSC-rich samples are required. A better understandingof telomerase regulation in this population may allow effectivetargeting of the telomerase enzyme complex using small moleculeinhibitors or additional novel approaches.
Disclosure of potential conflicts of interest is found at theend of this article.
Stem Cells Vol. 25 No. 8 August 2007, pp. 1853 -1861. OPEN ACCESS ARTICLE.