Analysis of telomere length in mantle cell lymphoma

Cottliar, Alejandra; Panero, Julieta; Pedrazzini, Estela; Noriega, Maria Fernanda; Narbaitz, Marina; Rodríguez, Antonio E. Pérez; Slavutsky, Irma

doi:10.1111/j.1600-0609.2009.01313.x

Cited by 11 publications

(8 citation statements)

References 32 publications

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“…In lymphoid malignancies, an association between short TL and chromosomal abnormalities or increased frequency of telomeric associations was reported in multiple myeloma [21,26], but no difference in TL between cases with normal and abnormal karyotypes or according to different genomic aberrations in patients with mantle cell lymphoma was found [27,28]. Our results in CLL support a role for telomere shortening at the origin of genomic instability [24] and reinforce previous reports showing the adverse prognostic value of chromosome alterations in this pathology [6,8,29].…”

Section: Discussionsupporting

confidence: 87%

Telomere shortening associated with increased genomic complexity in chronic lymphocytic leukemia

et al. 2015

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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.

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Section: Discussionsupporting

confidence: 87%

Telomere shortening associated with increased genomic complexity in chronic lymphocytic leukemia

et al. 2015

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“…Interestingly in one case, the longer of the two peaks, presumably corresponding to benign cells was lost at the time of relapse (Remes et al, 2000). Short telomeres have been documented in a series of MCL cases, and the same group have also shown short telomeres in FL-NHL and secondary DLBCL and that furthermore, these shortened telomeres correspond with the BCL2 mutational status of these lymphomas (Cottliar et al, 2009). …”

Section: B-cell Lymphomasmentioning

confidence: 89%

Telomere dysfunction and its role in haematological cancer

Jones¹,

Pepper²,

Baird

2012

Br J Haematol

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SummaryObservations in human tumours, as well as mouse models, have indicated that telomere dysfunction may be a key event driving genomic instability and disease progression in many solid tumour types. In this scenario, telomere shortening ultimately results in telomere dysfunction, fusion and genomic instability, creating the large-scale rearrangements that are characteristic of these tumours. It is now becoming apparent that this paradigm may also apply to haematological malignancies; indeed these conditions have provided some of the most convincing evidence of telomere dysfunction in any malignancy. Telomere length has been shown in several malignancies to provide clinically useful prognostic information, implicating telomere dysfunction in disease progression. In these malignancies extreme telomere shortening, telomere dysfunction and fusion have all been documented and correlate with the emergence of increased genomic complexity. Telomeres may therefore represent both a clinically useful prognostic tool and a potential target for therapeutic intervention.

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“…However, there is much evidence that telomere length is shorter in lymphoma cells (20-22). As a consequence, if tumor cells were circulating in the blood of undiagnosed patients, the average telomere length of their peripheral white blood cell DNA would tend to be shorter, not longer.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Study of Telomere Length Measured by Monochrome Multiplex Quantitative PCR and Risk of Non-Hodgkin Lymphoma

Lan

Cawthon

Shen

et al. 2009

Clinical Cancer Research

101

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Purpose: Telomere length plays an important role in the maintenance of chromosomal stability and in tumorigenesis. We hypothesized that telomere length in peripheral WBC DNA obtained from healthy individuals would be a predictor of future risk of developing non-Hodgkin lymphoma. Experimental Design: Using a new assay to measure relative telomere length, monochrome multiplex quantitative PCR, which strongly correlates with telomere length measured by Southern blot (Spearman r = 0.91, P < 0.0001) and has high precision (coefficient of variation = 7%), we compared telomere length in peripheral WBC DNA in 107 incident male non-Hodgkin lymphoma cases and 107 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Results: Median (10th, 90th percentile) telomere length was 1.10 (0.79, 1.43) in cases and 1.02 (0.78, 1.26) in controls (P = 0.0017, Wilcoxon sign test). There was a strong dose-response relationship between quartiles of telomere length and risk of nonHodgkin lymphoma overall [odds ratios (95% confidence intervals) by quartile: 1.0; 1.1 (0.4-2.7); 1.8 (0.7-4.9); and 3.6 (1.4-8.9); P trend = 0.003], and this association was similar across the most common non-Hodgkin lymphoma subtypes present in this study. Conclusion: These results suggest that longer telomere length may be a potential predictor for future risk of non-Hodgkin lymphoma. (Clin Cancer Res 2009;15(23):7429-33) Telomeres are complexes of tandem repeats of the sequence TTAGGG that cap chromosomes. They are essential for protecting chromosomal integrity (1), and shorten after every cell division. Short telomere length can cause genomic instability, which is associated with the initiation and progression of human cancers (2). At the same time, many incipient tumors can terminate their own growth by shortening their telomeres sufficiently to trigger replicative senescence or apoptosis (3). However, if sufficient numbers of mutations that promote growth and block cell senescence and apoptotic pathways accumulate in a cell before its telomeres shorten enough to trigger senescence or apoptosis and protect it from cancer, then unlimited proliferation may ensue. It follows that in some cell types, under some circumstances, long telomeres may actually increase the risk of cancer, by allowing more time and more cell divisions during which the cell can accumulate oncogenic mutations.Most epidemiologic studies have reported that relatively shorter telomere length measured in peripheral WBC and in some instances buccal cells is associated with increased risk of cancer (4-10). In contrast, some recent reports have suggested that longer telomere length may be associated with increased risk of certain tumors, such as breast cancer and melanoma (11,12). Most studies have used a case-control design (4-8), with several more recent reports using a prospective cohort design (9-11).Given that peripheral WBC contain lymphocyte subsets that derive from lymphocytic stem cells and immunologically active tissue, we...

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Analysis of telomere length in mantle cell lymphoma

Cited by 11 publications

References 32 publications

Telomere shortening associated with increased genomic complexity in chronic lymphocytic leukemia

Telomere shortening associated with increased genomic complexity in chronic lymphocytic leukemia

Telomere dysfunction and its role in haematological cancer

A Prospective Study of Telomere Length Measured by Monochrome Multiplex Quantitative PCR and Risk of Non-Hodgkin Lymphoma

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