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Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications
The immunoglobulin V(H) gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V(H) genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V(H)...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2003
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377180/ https://www.ncbi.nlm.nih.gov/pubmed/12592375 http://dx.doi.org/10.1038/sj.bjc.6600763 |
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author | Hultdin, M Rosenquist, R Thunberg, U Tobin, G Norrback, K-F Johnson, A Sundström, C Roos, G |
author_facet | Hultdin, M Rosenquist, R Thunberg, U Tobin, G Norrback, K-F Johnson, A Sundström, C Roos, G |
author_sort | Hultdin, M |
collection | PubMed |
description | The immunoglobulin V(H) gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V(H) genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V(H) genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and V(H) gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between V(H) gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 6.3 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months). Furthermore, the Ig gene sequence data revealed that samples with high mutations frequency (>6%) had long telomeres (∼8 kbp). Thus, both the telomere and V(H) gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction. |
format | Text |
id | pubmed-2377180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23771802009-09-10 Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications Hultdin, M Rosenquist, R Thunberg, U Tobin, G Norrback, K-F Johnson, A Sundström, C Roos, G Br J Cancer Genetics and Genomics The immunoglobulin V(H) gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V(H) genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V(H) genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and V(H) gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between V(H) gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 6.3 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months). Furthermore, the Ig gene sequence data revealed that samples with high mutations frequency (>6%) had long telomeres (∼8 kbp). Thus, both the telomere and V(H) gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction. Nature Publishing Group 2003-02-24 2003-02-18 /pmc/articles/PMC2377180/ /pubmed/12592375 http://dx.doi.org/10.1038/sj.bjc.6600763 Text en Copyright © 2003 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Genetics and Genomics Hultdin, M Rosenquist, R Thunberg, U Tobin, G Norrback, K-F Johnson, A Sundström, C Roos, G Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications |
title | Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications |
title_full | Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications |
title_fullStr | Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications |
title_full_unstemmed | Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications |
title_short | Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications |
title_sort | association between telomere length and v(h) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377180/ https://www.ncbi.nlm.nih.gov/pubmed/12592375 http://dx.doi.org/10.1038/sj.bjc.6600763 |
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