Concise review: Telomere biology in normal and leukemic hematopoietic stem cells.
The measurement of telomere length can give an insight into the replicative history of the cells in question. Much of the observed telomere loss occurs at the stem and progenitor cell level, even though these populations express the enzyme telomerase. Telomerase-transfected hematopoietic stem cells (HSC), although able to maintain telomere length, are still limited in terms of ability to undergo sequential transplantation, and other factors require to be addressed to achieve optimal levels of stem cell expansion. Unchecked telomere loss by HSC, meanwhile, would appear to play a significant role in the pathogenesis of bone marrow failure, as observed in the condition dyskeratosis congenita. This heterogeneous inherited condition appears to exhibit telomerase dysfunction as a common final pathogenic mechanism. Although less well-established for acquired marrow failure syndromes, mutations in key telomerase components have been described. The identification of the leukemic stem cell (LSC), along with the desire to target this population with anti-leukemia therapy, demands that telomerase biology be fully understood in this cell compartment. Future studies using primary selected LSC-rich samples are required. A better understanding of telomerase regulation in this population may allow effective targeting of the telomerase enzyme complex using small molecule inhibitors or additional novel approaches. Disclosure of potential conflicts of interest is found at the end of this article.
Drummond
Mark W
MW
Department of Haematology, Western Infirmary, Glasgow, UK. Mark.drummond@northglasgow.scot.nhs.uk
Balabanov
Stefan
S
Holyoake
Tessa L
TL
Brummendorf
Tim H
TH
D000208:Acute Disease; D000818:Animals; D049109:Cell Proliferation; D004261:DNA Replication / Q000502:physiology; D004273:DNA, Neoplasm / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009436:Neural Tube Defects / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016615:Telomere / Q000378:metabolism / Q000502:physiology*
D004273:DNA, Neoplasm; D019098:Telomerase