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Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma

SIMPLE SUMMARY: Multiple myeloma (MM) remains an incurable blood cancer. One of the current challenges in patient management is the risk assessment and subsequent treatment management for each patient with MM. Patients with an identical diagnosis may present very different disease courses and outcom...

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Autores principales: Rangel-Pozzo, Aline, Yu, Pak Lok Ivan, LaL, Sadhana, Asbaghi, Yasmin, Sisdelli, Luiza, Tammur, Pille, Tamm, Anu, Punab, Mari, Klewes, Ludger, Louis, Sherif, Knecht, Hans, Olujohungbe, Adebayo, Mai, Sabine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073772/
https://www.ncbi.nlm.nih.gov/pubmed/33921898
http://dx.doi.org/10.3390/cancers13081969
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author Rangel-Pozzo, Aline
Yu, Pak Lok Ivan
LaL, Sadhana
Asbaghi, Yasmin
Sisdelli, Luiza
Tammur, Pille
Tamm, Anu
Punab, Mari
Klewes, Ludger
Louis, Sherif
Knecht, Hans
Olujohungbe, Adebayo
Mai, Sabine
author_facet Rangel-Pozzo, Aline
Yu, Pak Lok Ivan
LaL, Sadhana
Asbaghi, Yasmin
Sisdelli, Luiza
Tammur, Pille
Tamm, Anu
Punab, Mari
Klewes, Ludger
Louis, Sherif
Knecht, Hans
Olujohungbe, Adebayo
Mai, Sabine
author_sort Rangel-Pozzo, Aline
collection PubMed
description SIMPLE SUMMARY: Multiple myeloma (MM) remains an incurable blood cancer. One of the current challenges in patient management is the risk assessment and subsequent treatment management for each patient with MM. Patients with an identical diagnosis may present very different disease courses and outcomes. This challenge of MM is a current focus of the scientific and medical communities. In our research, we have used an imaging approach to determine the risk of MM patients to progressive/aggressive disease. Using three-dimensional (3D) imaging of telomeres, the ends of chromosomes, we report that specific telomeric profiles are associated with aggressive disease. ABSTRACT: The prognosis of multiple myeloma (MM), an incurable B-cell malignancy, has significantly improved through the introduction of novel therapeutic modalities. Myeloma prognosis is essentially determined by cytogenetics, both at diagnosis and at disease progression. However, for a large cohort of patients, cytogenetic analysis is not always available. In addition, myeloma patients with favorable cytogenetics can display an aggressive clinical course. Therefore, it is necessary to develop additional prognostic and predictive markers for this disease to allow for patient risk stratification and personalized clinical decision-making. Genomic instability is a prominent characteristic in MM, and we have previously shown that the three-dimensional (3D) nuclear organization of telomeres is a marker of both genomic instability and genetic heterogeneity in myeloma. In this study, we compared in a longitudinal prospective study blindly the 3D telomeric profiles from bone marrow samples of 214 initially treatment-naïve patients with either monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with a minimum follow-up of 5 years. Here, we report distinctive 3D telomeric profiles correlating with disease aggressiveness and patient response to treatment in MM patients, and also distinctive 3D telomeric profiles for disease progression in smoldering multiple myeloma patients. In particular, lower average intensity (telomere length, below 13,500 arbitrary units) and increased number of telomere aggregates are associated with shorter survival and could be used as a prognostic factor to identify high-risk SMM and MM patients.
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spelling pubmed-80737722021-04-27 Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma Rangel-Pozzo, Aline Yu, Pak Lok Ivan LaL, Sadhana Asbaghi, Yasmin Sisdelli, Luiza Tammur, Pille Tamm, Anu Punab, Mari Klewes, Ludger Louis, Sherif Knecht, Hans Olujohungbe, Adebayo Mai, Sabine Cancers (Basel) Article SIMPLE SUMMARY: Multiple myeloma (MM) remains an incurable blood cancer. One of the current challenges in patient management is the risk assessment and subsequent treatment management for each patient with MM. Patients with an identical diagnosis may present very different disease courses and outcomes. This challenge of MM is a current focus of the scientific and medical communities. In our research, we have used an imaging approach to determine the risk of MM patients to progressive/aggressive disease. Using three-dimensional (3D) imaging of telomeres, the ends of chromosomes, we report that specific telomeric profiles are associated with aggressive disease. ABSTRACT: The prognosis of multiple myeloma (MM), an incurable B-cell malignancy, has significantly improved through the introduction of novel therapeutic modalities. Myeloma prognosis is essentially determined by cytogenetics, both at diagnosis and at disease progression. However, for a large cohort of patients, cytogenetic analysis is not always available. In addition, myeloma patients with favorable cytogenetics can display an aggressive clinical course. Therefore, it is necessary to develop additional prognostic and predictive markers for this disease to allow for patient risk stratification and personalized clinical decision-making. Genomic instability is a prominent characteristic in MM, and we have previously shown that the three-dimensional (3D) nuclear organization of telomeres is a marker of both genomic instability and genetic heterogeneity in myeloma. In this study, we compared in a longitudinal prospective study blindly the 3D telomeric profiles from bone marrow samples of 214 initially treatment-naïve patients with either monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with a minimum follow-up of 5 years. Here, we report distinctive 3D telomeric profiles correlating with disease aggressiveness and patient response to treatment in MM patients, and also distinctive 3D telomeric profiles for disease progression in smoldering multiple myeloma patients. In particular, lower average intensity (telomere length, below 13,500 arbitrary units) and increased number of telomere aggregates are associated with shorter survival and could be used as a prognostic factor to identify high-risk SMM and MM patients. MDPI 2021-04-19 /pmc/articles/PMC8073772/ /pubmed/33921898 http://dx.doi.org/10.3390/cancers13081969 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rangel-Pozzo, Aline
Yu, Pak Lok Ivan
LaL, Sadhana
Asbaghi, Yasmin
Sisdelli, Luiza
Tammur, Pille
Tamm, Anu
Punab, Mari
Klewes, Ludger
Louis, Sherif
Knecht, Hans
Olujohungbe, Adebayo
Mai, Sabine
Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma
title Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma
title_full Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma
title_fullStr Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma
title_full_unstemmed Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma
title_short Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma
title_sort telomere architecture correlates with aggressiveness in multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073772/
https://www.ncbi.nlm.nih.gov/pubmed/33921898
http://dx.doi.org/10.3390/cancers13081969
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