Relevance of telomere/telomerase system impairment in early stage chronic lymphocytic leukemia. Issue 7 (4th April 2014)

• Record Type: Journal Article
• Authors: Hoxha, Mirjam; Fabris, Sonia; Agnelli, Luca; Bollati, Valentina; Cutrona, Giovanna; Matis, Serena; Recchia, Anna Grazia; Gentile, Massimo; Cortelezzi, Agostino; Morabito, Fortunato; Bertazzi, Pier Alberto; Ferrarini, Manlio; Neri, Antonino
• Is Part Of: Genes, chromosomes & cancer. Volume 53:Issue 7(2014:Jul.)
• Page Start: 612
• Page End: 621
• Publication Date: 2014-04-04
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22171
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Several studies have proposed telomere length and telomerase activity as prognostic factors in chronic lymphocytic leukemia (CLL), whereas information addressing the role of telomere‐associated genes is limited. We measured relative telomere length (RTL) and <italic>TERT</italic> expression levels in purified peripheral CD19<sup>+</sup> B‐cells from seven healthy donors and 77 untreated CLLs in early stage disease (Binet A). Data were correlated with the major biological and cytogenetic markers, global DNA methylation (<italic>Alu</italic> and <italic>LINE‐1</italic>), and clinical outcome. The expression profiles of telomere‐associated genes were also investigated. RTL was decreased in CLLs as compared with controls (<italic>P</italic> < 0.001); within CLL, a progressive and significant RTL shortening was observed in patients from 13q‐ through +12, 11q‐, and 17p‐ alterations; short telomeres were significantly associated with unmutated <italic>IGHV</italic> configuration and global DNA hypomethylation. Decreased RTL was associated with a shorter time to first treatment. A significant upregulation of <italic>POT1</italic>, <italic>TRF1</italic>, <italic>RAP1</italic>, <italic>MRE11A</italic>, <italic>RAD50</italic>, and <italic>RPA1</italic> transcript levels was observed in CLLs compared with controls. Our study suggests that impairment of telomere/telomerase system represents an early event in CLL pathogenesis. Moreover, the correlation between telomere shortening and global DNA hypomethylation supports the involvement of DNA hypomethylation to increase chromosome instability. © 2014 Wiley Periodicals, Inc.</p> </abstract>