Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept

Monitoring measurable residual disease (MRD) is crucial to assess treatment response in Multiple Myeloma (MM). Detection of MRD in peripheral blood (PB) by exploring Extracellular Vesicles (EVs), and their cargo, would allow frequent and minimally invasive monitoring of MM. This work aims to detect...

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Main Authors: Rui Bergantim, Sara Peixoto da Silva, Bárbara Polónia, Mélanie A. G. Barbosa, André Albergaria, Jorge Lima, Hugo R. Caires, José E. Guimarães, M. Helena Vasconcelos
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/22/13686
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author Rui Bergantim
Sara Peixoto da Silva
Bárbara Polónia
Mélanie A. G. Barbosa
André Albergaria
Jorge Lima
Hugo R. Caires
José E. Guimarães
M. Helena Vasconcelos
author_facet Rui Bergantim
Sara Peixoto da Silva
Bárbara Polónia
Mélanie A. G. Barbosa
André Albergaria
Jorge Lima
Hugo R. Caires
José E. Guimarães
M. Helena Vasconcelos
author_sort Rui Bergantim
collection DOAJ
description Monitoring measurable residual disease (MRD) is crucial to assess treatment response in Multiple Myeloma (MM). Detection of MRD in peripheral blood (PB) by exploring Extracellular Vesicles (EVs), and their cargo, would allow frequent and minimally invasive monitoring of MM. This work aims to detect biomarkers of MRD in EVs isolated from MM patient samples at diagnosis and remission and compare the MRD-associated content between BM and PB EVs. EVs were isolated by size-exclusion chromatography, concentrated by ultrafiltration, and characterized according to their size and concentration, morphology, protein concentration, and the presence of EV-associated protein markers. EVs from healthy blood donors were used as controls. It was possible to isolate EVs from PB and BM carrying MM markers. Diagnostic samples had different levels of MM markers between PB and BM paired samples, but no differences between PB and BM were found at remission. EVs concentration was lower in the PB of healthy controls than of patients, and MM markers were mostly not detected in EVs from controls. This study pinpoints the potential of PB EVs from MM remission patients as a source of MM biomarkers and as a non-invasive approach for monitoring MRD.
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spelling doaj.art-0a8b79b3c6be42ddb5a09a8a41fafbdf2023-11-24T08:31:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221368610.3390/ijms232213686Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of ConceptRui Bergantim0Sara Peixoto da Silva1Bárbara Polónia2Mélanie A. G. Barbosa3André Albergaria4Jorge Lima5Hugo R. Caires6José E. Guimarães7M. Helena Vasconcelos8i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugali3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, PortugalMonitoring measurable residual disease (MRD) is crucial to assess treatment response in Multiple Myeloma (MM). Detection of MRD in peripheral blood (PB) by exploring Extracellular Vesicles (EVs), and their cargo, would allow frequent and minimally invasive monitoring of MM. This work aims to detect biomarkers of MRD in EVs isolated from MM patient samples at diagnosis and remission and compare the MRD-associated content between BM and PB EVs. EVs were isolated by size-exclusion chromatography, concentrated by ultrafiltration, and characterized according to their size and concentration, morphology, protein concentration, and the presence of EV-associated protein markers. EVs from healthy blood donors were used as controls. It was possible to isolate EVs from PB and BM carrying MM markers. Diagnostic samples had different levels of MM markers between PB and BM paired samples, but no differences between PB and BM were found at remission. EVs concentration was lower in the PB of healthy controls than of patients, and MM markers were mostly not detected in EVs from controls. This study pinpoints the potential of PB EVs from MM remission patients as a source of MM biomarkers and as a non-invasive approach for monitoring MRD.https://www.mdpi.com/1422-0067/23/22/13686multiple myelomaextracellular vesiclesmeasurable residual diseaseliquid biopsy
spellingShingle Rui Bergantim
Sara Peixoto da Silva
Bárbara Polónia
Mélanie A. G. Barbosa
André Albergaria
Jorge Lima
Hugo R. Caires
José E. Guimarães
M. Helena Vasconcelos
Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept
International Journal of Molecular Sciences
multiple myeloma
extracellular vesicles
measurable residual disease
liquid biopsy
title Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept
title_full Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept
title_fullStr Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept
title_full_unstemmed Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept
title_short Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept
title_sort detection of measurable residual disease biomarkers in extracellular vesicles from liquid biopsies of multiple myeloma patients a proof of concept
topic multiple myeloma
extracellular vesicles
measurable residual disease
liquid biopsy
url https://www.mdpi.com/1422-0067/23/22/13686
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