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

Bergantim, Rui; Peixoto da Silva, Sara; Polónia, Bárbara; Barbosa, Mélanie A. G.; Albergaria, André; Lima, Jorge; Caires, Hugo R.; Guimarães, José E.; Vasconcelos, M. Helena

doi:10.3390/ijms232213686

Open AccessArticle

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

by

Rui Bergantim

^1,2,3,4,

Sara Peixoto da Silva

^1,2

,

Bárbara Polónia

^1,2,

Mélanie A. G. Barbosa

^1,2

,

André Albergaria

^1,5

,

Jorge Lima

^1,5

,

Hugo R. Caires

^1,2

,

José E. Guimarães

^1,2,3,4,6,* and

M. Helena Vasconcelos

^1,2,7,*

¹

i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal

²

Cancer Drug Resistance Group, IPATIMUP—Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal

³

Clinical Hematology, Hospital Center of São João, 4200-319 Porto, Portugal

⁴

Clinical Hematology, FMUP—Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal

⁵

Research Innovation Unit, Translational Research & Industry Partnerships Office, i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal

⁶

Instituto Universitário de Ciências da Saúde, Cooperativa de Ensino Superior Politécnico e Universitário IUCSESPU, 4585-116 Gandra-Paredes, Portugal

⁷

Department of Biological Sciences, FFUP—Faculty of Pharmacy of the University of Porto, 4050-313 Porto, Portugal

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2022, 23(22), 13686; https://doi.org/10.3390/ijms232213686

Submission received: 3 October 2022 / Revised: 3 November 2022 / Accepted: 4 November 2022 / Published: 8 November 2022

(This article belongs to the Special Issue Insights in New Biomarkers and Molecular Drug Targets in Hematological Neoplasias)

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Abstract

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.

Keywords: multiple myeloma; extracellular vesicles; measurable residual disease; liquid biopsy

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MDPI and ACS Style

Bergantim, R.; Peixoto da Silva, S.; Polónia, B.; Barbosa, M.A.G.; Albergaria, A.; Lima, J.; Caires, H.R.; Guimarães, J.E.; Vasconcelos, M.H. Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept. Int. J. Mol. Sci. 2022, 23, 13686. https://doi.org/10.3390/ijms232213686

AMA Style

Bergantim R, Peixoto da Silva S, Polónia B, Barbosa MAG, Albergaria A, Lima J, Caires HR, Guimarães JE, Vasconcelos MH. 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. 2022; 23(22):13686. https://doi.org/10.3390/ijms232213686

Chicago/Turabian Style

Bergantim, Rui, Sara Peixoto da Silva, Bárbara Polónia, Mélanie A. G. Barbosa, André Albergaria, Jorge Lima, Hugo R. Caires, José E. Guimarães, and M. Helena Vasconcelos. 2022. "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 23, no. 22: 13686. https://doi.org/10.3390/ijms232213686

APA Style

Bergantim, R., Peixoto da Silva, S., Polónia, B., Barbosa, M. A. G., Albergaria, A., Lima, J., Caires, H. R., Guimarães, J. E., & Vasconcelos, M. H. (2022). 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, 23(22), 13686. https://doi.org/10.3390/ijms232213686

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

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