Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Blood cell telomere length is a dynamic feature
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Show others and affiliations
2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 6, e21485- p.Article in journal (Refereed) Published
Abstract [en]

There is a considerable heterogeneity in blood cell telomere length (TL) for individuals of similar age and recent studies have revealed that TL changes by time are dependent on TL at baseline. TL is partly inherited, but results from several studies indicate that e.g. life style and/or environmental factors can affect TL during life. Collectively, these studies imply that blood cell TL might fluctuate during a life time and that the actual TL at a defined time point is the result of potential regulatory mechanism(s) and environmental factors. We analyzed relative TL (RTL) in subsequent blood samples taken six months apart from 50 individuals and found significant associations between RTL changes and RTL at baseline. Individual RTL changes per month were more pronounced than the changes recorded in a previously studied population analyzed after 10 years' follow up. The data argues for an oscillating TL pattern which levels out at longer follow up times. In a separate group of five blood donors, a marked telomere loss was demonstrated within a six month period for one donor where after TL was stabilized. PCR determined RTL changes were verified by Southern blotting and STELA (single telomere elongation length analysis). The STELA demonstrated that for the donor with a marked telomere loss, the heterogeneity of the telomere distribution decreased considerably, with a noteworthy loss of the largest telomeres. In summary, the collected data support the concept that individual blood cell telomere length is a dynamic feature and this will be important to recognize in future studies of human telomere biology.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science , 2011. Vol. 6, no 6, e21485- p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:umu:diva-57221DOI: 10.1371/journal.pone.0021485PubMedID: 21720548OAI: oai:DiVA.org:umu-57221DiVA: diva2:540520
Available from: 2012-07-10 Created: 2012-07-10 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Telomere length: dynamics and role as a biological marker in malignancy
Open this publication in new window or tab >>Telomere length: dynamics and role as a biological marker in malignancy
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Telomeres are protective structures at the end of our chromosomes, composed of multiple repeats of the DNA sequence TTAGGG. They are essential for maintaining chromosomal stability by preventing damage and degradation of the chromosome ends. Telomeres are normally shortened with each cell division until a critical length is reached, at which stage cell cycle arrest is induced. Telomere shortening can be prevented in the presence of the telomere-­‐elongating enzyme telomerase. Telomerase is expressed during embryogenesis and in certain normal cell types, but most somatic cells exhibit undetectable levels of telomerase activity. In contrast, most cancer cells express telomerase enabling them to proliferate indefinitely.

There is a search for reliable molecular markers that can be used to help predict cancer risk and outcome. The interest of investigating telomere length as a potential biomarker in malignancy has grown rapidly, and both tumors and normal tissues have been in focus for telomere length measurements. In this thesis, telomere length was investigated in breast cancer patients and in patients with renal cell carcinoma (RCC). The breast cancer patients were found to have significantly longer mean telomere length in peripheral blood cells (i.e. immune cells) compared to a tumor-­‐free control group. Moreover, patients with the longest blood telomere length had a significantly worse outcome compared to patients with shorter blood telomeres. In a patient group with clear cell RCC, telomere length was investigated in peripheral blood cells, in tumors and in corresponding kidney cortex. Again, patients with the longest blood telomere length had a significantly worse prognosis compared to those with shorter blood telomeres. In contrast, telomere length in tumor and kidney cortex tissues did not predict outcome per se.

Immunological components may play a role in telomere length dynamics as well as in cancer development. We aimed to investigate a possible association between telomere length and certain immunological parameters, including various cytokines and peripheral levels of a blood cell type with suppressor function [regulatory T cells (Tregs)]. In our patients with clear cell RCC, three cytokines correlated significantly with tumor telomere length, but not with telomere length in peripheral blood cells. In a separate patient group with various RCC tumors, blood telomere length correlated positively with the amount of Tregs. It might be speculated that a subset of patients with long blood telomeres has a less efficient immune response due to high Treg levels, contributing to a worse prognosis.

Another aim of this thesis was to explore telomere length changes over time. Evaluation of blood samples collected at a 6-­‐month interval from 50 individuals, showed that half of the participants experienced a decline in mean telomere length during the time period. This group had longer telomere length at baseline compared to those who demonstrated increased/stable telomere length. In a separate group of five blood donors, a remarkable drop in telomere length was detected in one donor over a 6-­‐month period, whereas the other donors exhibited only small fluctuations in telomere length.

In conclusion, the results of this thesis indicate that blood telomere length has potential to act as an independent prognostic marker in malignancy. Adding to the complexity is the fact that changes in blood telomere length might occur within relatively short time spans, indicating that telomere length is a dynamic character. 

Place, publisher, year, edition, pages
Umeå: Umeå University, 2012. 53 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1522
Keyword
Telomere length, peripheral blood, immune cells, breast cancer, renal cell carcinoma, biological marker
National Category
Medical and Health Sciences
Research subject
Pathology
Identifiers
urn:nbn:se:umu:diva-61549 (URN)978-91-7459-481-2 (ISBN)
Public defence
2012-12-14, Sal B, 9tr, By 1D - Tandläkarhögskolan, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2012-11-23 Created: 2012-11-19 Last updated: 2012-12-16Bibliographically approved

Open Access in DiVA

fulltext(910 kB)142 downloads
File information
File name FULLTEXT02.pdfFile size 910 kBChecksum SHA-512
43322ddd988cf5be8ffcb49fecc32bcaceb2bec99f1ed937093f95fb303fa55a3c6a231bc70f89db5bcfe578366aa89dd532f0ebd73d02861c4cce3bfbb37566
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Svenson, UlrikaNordfjäll, KatarinaOsterman, PiaRoos, Göran
By organisation
Pathology
In the same journal
PLoS ONE
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 142 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 140 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf