title: Telomere shortening associated with increased genomic complexity in chronic lymphocytic leukemia.
abstract: Telomeric dysfunction has been proposed as an emerging prognostic factor in chronic lymphocytic leukemia (CLL). We have explored the relationship between telomere length (TL) and chromosome alterations studied by fluorescence in situ hybridization (FISH) and conventional cytogenetics in 107 newly diagnosed CLL patients; 61 normal controls were also evaluated. Results were correlated with clinical parameters and outcome. Absolute TL measurement was carried out on DNA samples by real-time quantitative PCR. A significant telomere shortening in patients compared to controls was observed (p = 0.0001). The analysis taking into account FISH risk groups showed shorter TLs in cases with del11q/17p compared to patients with 13q14 deletion as a single alteration (p = 0.0037), no alterations (NA) (p = 0.028), and cases with abnormal karyotypes (p = 0.014). In addition, a significant TL reduction in cases with two or more anomalies with respect to those with NA (p = 0.033) and with one alteration (p = 0.045), and no differences compared to cases with deletions 11q/17p were observed. Patients with only one anomaly did not show statistical differences with respect to controls; meanwhile, a significant TL reduction in cases with two or more aberrations was observed (p = 0.025). The shortest telomeres were associated to 11q/17p deletion with significant differences compared to the remaining groups (p ≤ 0.045). Significantly shorter treatment free survival in patients with two or more alterations compared to those with NA plus one abnormality was observed (p = 0.0006). Our findings support the association between short TL and chromosome alterations in CLL and indicate the importance of telomere dysfunction in driving genomic instability in this pathology.
authors.affiliation: Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, J.A. Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Dos Santos
authors.affiliation: Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, J.A. Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina.
authors.forename: Julieta
authors.initials: J
authors.lastname: Panero
authors.affiliation: Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, J.A. Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Palau Nagore
authors.affiliation: División Patología Molecular, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Carmen
authors.initials: C
authors.lastname: Stanganelli
authors.affiliation: Servicio de Hematología, Hospital General de Agudos "Dr Teodoro Álvarez", Buenos Aires, Argentina.
authors.forename: Raimundo F
authors.initials: RF
authors.lastname: Bezares
authors.affiliation: Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, J.A. Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina. islavutsky@hematologia.anm.edu.ar.
authors.forename: Irma
authors.initials: I
authors.lastname: Slavutsky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D015894:Genome, Human; D042822:Genomic Instability; D023281:Genomics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016615:Telomere / Q000235:genetics*; D059506:Telomere Shortening / Q000235:genetics*
keywords: Chronic lymphocytic leukemia; Cytogenetics; FISH; Telomere length