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Published on: April 13, 2015
Telomere shortening in patients with plasma cell disorders
Alejandra Cottliar1, Estela Pedrazzini, Claudia Corrado
1Departamento de Genética, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina. acottliar@yahoo.com.ar
Objectives:
Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).
Methods:
Thirty-one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight at remission (RE) and two cases with MGUS were studied. TL based on terminal restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular cytogenetic analyses were performed. Telomeric associations (TAs) on BM metaphases were also studied.
Results:
TRF analysis in total MM patients showed a mean TRF peak value (5.20 +/- 0.35 kb) shorter than those observed in controls (8.5 +/- 0.5 kb) (P < 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P < 0.001), with TL restored at RE. A strong correlation with the percentage of BM plasma cell infiltration (BMPCI) (rK = -0.540; P = 0.002) was found. Patients with abnormal karyotypes (AK) had significantly shorter TRFs than that observed in MM patients with normal karyotypes (P < 0.05). TRFs in MGUS patients did not differ with respect to controls. TA analysis showed an increased percentage in MM (19.46 +/- 1.98%) with respect to MGUS (6.12 +/- 1.87%) and normal BM cells (2.00 +/- 0.93%) (P < 0.001).
Conclusions:
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.
Insights
Multiple myeloma patients exhibit significantly shortened telomere length (TL), correlating with disease progression and abnormal karyotypes. Telomere length is restored in remission, suggesting a link to clinical evolution.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Telomeres are crucial for chromosomal integrity, and their shortening is linked to genomic instability.
- Understanding telomere dynamics in hematological malignancies like multiple myeloma (MM) is vital for prognosis.
Purpose of the Study:
- To investigate telomere length (TL) in bone marrow (BM) cells of patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).
- To explore the relationship between TL, disease status, and cytogenetic abnormalities in MM.
Main Methods:
- Terminal restriction fragment (TRF) assay was used to evaluate TL in 31 MM patients (at diagnosis, relapse, remission) and 2 MGUS cases.
- Cytogenetic, molecular cytogenetic analyses, and telomeric associations (TAs) on BM metaphases were performed.
Main Results:
- MM patients showed significantly shorter mean TRF values compared to controls (5.20 vs. 8.5 kb).
- Telomere shortening was pronounced at diagnosis and relapse, with restoration in remission, correlating with BM plasma cell infiltration and abnormal karyotypes.
- Increased telomeric associations were observed in MM patients compared to MGUS and normal controls.
Conclusions:
- Reduced TL in MM, particularly with high plasma cell infiltration and abnormal karyotypes, suggests a role in disease progression.
- Telomere shortening appears to contribute to increased telomeric associations and chromosomal instability in MM.
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