Telomere shortening in patients with plasma cell disorders

Cottliar, Alejandra; Pedrazzini, Estela; Corrado, Claudia; Engelberger, María Inés; Narbaitz, Marina; Slavutsky, Irma

doi:10.1034/j.1600-0609.2003.00157.x

Cited by 30 publications

(33 citation statements)

References 29 publications

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“…As we have previously reported (17), all patients showed significant telomere shortening (MGUS: 6.55 ± 0.45 kb and MM: 6.39 ± 0.52 kb) compared with controls (8.12 ± 0.26 kb) (P = 0.003 and P = 0.004, respectively) ( Figure 1). However, when the analysis of TL was performed according to hTERT groups, we found that patients from GIII, with the highest telomerase expression, had the shortest TL (Table 2).…”

Section: Tl Evaluationsupporting

confidence: 57%

“…A number of reported studies have evaluated TL and telomerase activity in MM patients (15)(16)(17)(18)(19). However, information is very scarce regarding telomere dysfunction in patients with MGUS (15,17) (five and two patients, respectively), and no studies about changes in the expression of shelterin proteins in plasma cell disorders have been reported.…”

Section: Introductionmentioning

confidence: 99%

“…Telomere length was evaluated by use of terminal restriction fragments (TRF) assay as previously described (17). Briefly, for terminal restriction analysis, high molecular weight DNA was extracted from BM samples, followed by double digestion of 10 μg DNA with HinfI and RsaI restriction enzymes at 37ºC, overnight.…”

Section: Telomere Length Evaluationmentioning

confidence: 99%

See 2 more Smart Citations

Altered mRNA Expression of Telomere-Associated Genes in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Panero

Arbelbide

Fantl

et al. 2010

Mol Med

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In this study, we explored changes in the expression of the telomere maintenance genes, TRF1, TRF2 and TANK1 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Results were correlated with human telomerase reverse transcriptase (hTERT ) expression, telomere length (TL) and clinicopathological characteristics. Bone marrow (BM) samples from 132 patients, 64 with MGUS and 68 with MM, were studied. Real-time quantitative reverse transcription-polymerase chain reaction was used to quantify gene expression. TL was evaluated by terminal restriction fragment length analysis. MGUS patients showed increased TRF1 levels (P = 0.006) and lower expression of TRF2 (P = 0.005) and TANK1 (P = 0.003) compared with MM patients. For hTERT analysis, patients were divided into three groups by use of receiver operating characteristics: low (group I [GI]), intermediate (group II [GII]) and high (group III [GIII]) expression. We observed increasing expression of TRF2 and TANK1 from GI to GIII in MGUS and MM, with differences for both genes in MM (P < 0.01) and for TRF2 in MGUS (P < 0.01). GIII patients with the highest telomerase expression had the shortest TL. In both entities, a positive association between TRF2-TANK1, TRF2-hTERT and TANK1-hTERT (P ≤ 0.01) was observed. In MM, the percentage of BM infiltration and Ki-67 index were positively associated with TRF2, TANK1 and hTERT expression (P ≤ 0.03) and negatively with TL (P = 0.02), whereas lactate dehydrogenase was significantly correlated with TRF2 mRNA (P = 0.008). Our findings provide the first evidence of a modification in the expression of telomeric proteins in plasma cell disorders, and suggest that mechanisms other than telomerase activation are involved in TL maintenance in these pathologies.

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Section: Tl Evaluationsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Altered mRNA Expression of Telomere-Associated Genes in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Panero

Arbelbide

Fantl

et al. 2010

Mol Med

Self Cite

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show abstract

“…Other data demonstrate that telomere attrition is a common early alteration in many human cancers, including gastric cancer (45,46), colon cancer (47), lung cancer (48), and breast cancer (6,49). Telomere dysfunction is also associated with bone marrow failure (50), specifically MGUS and multiple myeloma (51,52). Very short telomeres are also associated with CLL (53), dyskeratosis congenita (54), pancreatic cancer (55), prostate cancer (9), and Barrett's esophagus, which is associated with an increased risk of esophageal adenocarcinoma (56).…”

Section: Discussionmentioning

confidence: 99%

Novel automated three‐dimensional genome scanning based on the nuclear architecture of telomeres

Klewes

Höbsch

Katzir³

et al. 2010

Cytometry Pt A

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Telomeres, the end of chromosomes, are organized in a nonoverlapping fashion and form microterritories in nuclei of normal cells. Previous studies have shown that normal and tumor cell nuclei differ in their 3D telomeric organization. The differences include a change in the spatial organization of the telomeres, in telomere numbers and sizes and in the presence of telomeric aggregates. Previous attempts to identify the above parameters of 3D telomere organization were semi-automated. Here we describe the automation of 3D scanning for telomere signatures in interphase nuclei based on three-dimensional fluorescent in situ hybridization (3D-FISH) and, for the first time, define its sensitivity in tumor cell detection. The data were acquired with a highthroughput scanning/acquisition system that allows to measure cells and acquire 3D images of nuclei at high resolution with 403 or 603 oil and at a speed of 10,000-15,000 cells h 21 , depending on the cell density on the slides. The automated scanning, TeloScan, is suitable for large series of samples and sample sizes. We define the sensitivity of this automation for tumor cell detection. The data output includes 3D telomere positions, numbers of telomeric aggregates, telomere numbers, and telomere signal intensities. We were able to detect one aberrant cell in 1,000 normal cells. In conclusions, we are able to detect tumor cells based on 3D architectural profiles of the genome. This new tool could, in the future, assist in patient diagnosis, in the detection of minimal residual disease, in the analysis of treatment response and in treatment decisions. '

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“…TL in MM cells has been shown to be reduced compared to patient-matched leucocytes and normal age-matched controls, and was shorter still in patients with relapsed disease (Cottliar et al, 2003;Wu et al, 2003). In addition, there appears to be a stabilization of telomeres in the shorter length ranges below 5AE5 kb.…”

Section: Multiple Myeloma (Mm)mentioning

confidence: 96%

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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Telomere shortening in patients with plasma cell disorders

Abstract: MM patients showed a significant reduction in TL (> 60% of BMPCI and AK), suggesting a probable association with clinical evolution. Moreover, our findings support the idea that telomere shortening usually leads to increased frequencies of TAs and chromosome instability.

Cited by 30 publications

References 29 publications

Altered mRNA Expression of Telomere-Associated Genes in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Altered mRNA Expression of Telomere-Associated Genes in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Novel automated three‐dimensional genome scanning based on the nuclear architecture of telomeres

Telomere dysfunction and its role in haematological cancer

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