Telomere dysfunction and its role in haematological cancer
- 11 January 2012
- journal article
- review article
- Published by Wiley in British Journal of Haematology
- Vol. 156 (5), 573-587
- https://doi.org/10.1111/j.1365-2141.2011.09022.x
Abstract
Observations in human tumours, as well as mouse models, have indicated that telomere dysfunction may be a key event driving genomic instability and disease progression in many solid tumour types. In this scenario, telomere shortening ultimately results in telomere dysfunction, fusion and genomic instability, creating the large-scale rearrangements that are characteristic of these tumours. It is now becoming apparent that this paradigm may also apply to haematological malignancies; indeed these conditions have provided some of the most convincing evidence of telomere dysfunction in any malignancy. Telomere length has been shown in several malignancies to provide clinically useful prognostic information, implicating telomere dysfunction in disease progression. In these malignancies extreme telomere shortening, telomere dysfunction and fusion have all been documented and correlate with the emergence of increased genomic complexity. Telomeres may therefore represent both a clinically useful prognostic tool and a potential target for therapeutic intervention.Keywords
This publication has 120 references indexed in Scilit:
- Subtelomeric regions in mammalian cells are deficient in DNA double-strand break repairDNA Repair, 2011
- Telomere deregulations possess cytogenetic, phenotype, and prognostic specificities in acute leukemiasExperimental Hematology, 2011
- Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemiaProceedings of the National Academy of Sciences of the United States of America, 2009
- Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenitaProceedings of the National Academy of Sciences of the United States of America, 2008
- Telomerase inhibitor GRN163L inhibits myeloma cell growth in vitro and in vivoLeukemia, 2008
- The role of telomere biology in bone marrow failure and other disordersMechanisms of Ageing and Development, 2008
- Telomere Length and Mortality: A Study of Leukocytes in Elderly Danish TwinsAmerican Journal of Epidemiology, 2008
- A DNA damage checkpoint response in telomere-initiated senescenceNature, 2003
- Extensive allelic variation and ultrashort telomeres in senescent human cellsNature Genetics, 2003
- Telomeres shorten during ageing of human fibroblastsNature, 1990