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Relevance of telomere/telomerase system impairment in early stage chronic lymphocytic leukemia
Author(s) -
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
Publication year - 2014
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22171
Subject(s) - telomere , telomerase , ighv@ , biology , chronic lymphocytic leukemia , rad50 , chromosome instability , cancer research , germline , dna methylation , chromosome , gene , microbiology and biotechnology , genetics , leukemia , gene expression , dna binding protein , transcription factor
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 TERT expression levels in purified peripheral CD19 + 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 ( Alu and LINE‐1 ), and clinical outcome. The expression profiles of telomere‐associated genes were also investigated. RTL was decreased in CLLs as compared with controls ( P < 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 IGHV configuration and global DNA hypomethylation. Decreased RTL was associated with a shorter time to first treatment. A significant upregulation of POT1 , TRF1 , RAP1 , MRE11A , RAD50 , and RPA1 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.