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Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma

Introduction. Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells (MM cells) in the bone-marrow (BM) compartment. BM mesenchymal stromal cells (MSC) from newly diagnosed MM patients were shown to be involved in MM pathogenesis and chemoresistance. T...

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Autores principales: Lemaitre, Léa, Do Souto Ferreira, Laura, Joubert, Marie-Véronique, Avet-Loiseau, Hervé, Martinet, Ludovic, Corre, Jill, Couderc, Bettina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312921/
https://www.ncbi.nlm.nih.gov/pubmed/32481768
http://dx.doi.org/10.3390/ijms21113854
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author Lemaitre, Léa
Do Souto Ferreira, Laura
Joubert, Marie-Véronique
Avet-Loiseau, Hervé
Martinet, Ludovic
Corre, Jill
Couderc, Bettina
author_facet Lemaitre, Léa
Do Souto Ferreira, Laura
Joubert, Marie-Véronique
Avet-Loiseau, Hervé
Martinet, Ludovic
Corre, Jill
Couderc, Bettina
author_sort Lemaitre, Léa
collection PubMed
description Introduction. Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells (MM cells) in the bone-marrow (BM) compartment. BM mesenchymal stromal cells (MSC) from newly diagnosed MM patients were shown to be involved in MM pathogenesis and chemoresistance. The patients displayed a distinct transcriptome and were functionally different from healthy donors’ (HD) MSC. Our aim was to determine whether MM–MSC also contributed to relapse. Methods. We obtained and characterized patients’ MSC samples at diagnosis, two years after intensive treatment, without relapse and at relapse. Results. Transcriptomic analysis revealed differences in gene expression between HD and MM-MSC, whatever the stage of the disease. An easier differentiation towards adipogenesis at the expense of osteoblatogeneis was observed, even in patients displaying a complete response to treatment. Although their transcriptome was similar, we found that MSC from relapsed patients had an increased immunosuppressive ability, compared to those from patients in remission. Conclusion. We demonstrated that imprinting of MSC transcriptome demonstrated at diagnosis of MM, persisted even after the apparent disappearance of MM cells induced by treatment, suggesting the maintenance of a local context favorable to relapse.
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spelling pubmed-73129212020-06-29 Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma Lemaitre, Léa Do Souto Ferreira, Laura Joubert, Marie-Véronique Avet-Loiseau, Hervé Martinet, Ludovic Corre, Jill Couderc, Bettina Int J Mol Sci Article Introduction. Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells (MM cells) in the bone-marrow (BM) compartment. BM mesenchymal stromal cells (MSC) from newly diagnosed MM patients were shown to be involved in MM pathogenesis and chemoresistance. The patients displayed a distinct transcriptome and were functionally different from healthy donors’ (HD) MSC. Our aim was to determine whether MM–MSC also contributed to relapse. Methods. We obtained and characterized patients’ MSC samples at diagnosis, two years after intensive treatment, without relapse and at relapse. Results. Transcriptomic analysis revealed differences in gene expression between HD and MM-MSC, whatever the stage of the disease. An easier differentiation towards adipogenesis at the expense of osteoblatogeneis was observed, even in patients displaying a complete response to treatment. Although their transcriptome was similar, we found that MSC from relapsed patients had an increased immunosuppressive ability, compared to those from patients in remission. Conclusion. We demonstrated that imprinting of MSC transcriptome demonstrated at diagnosis of MM, persisted even after the apparent disappearance of MM cells induced by treatment, suggesting the maintenance of a local context favorable to relapse. MDPI 2020-05-28 /pmc/articles/PMC7312921/ /pubmed/32481768 http://dx.doi.org/10.3390/ijms21113854 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lemaitre, Léa
Do Souto Ferreira, Laura
Joubert, Marie-Véronique
Avet-Loiseau, Hervé
Martinet, Ludovic
Corre, Jill
Couderc, Bettina
Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma
title Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma
title_full Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma
title_fullStr Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma
title_full_unstemmed Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma
title_short Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma
title_sort imprinting of mesenchymal stromal cell transcriptome persists even after treatment in patients with multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312921/
https://www.ncbi.nlm.nih.gov/pubmed/32481768
http://dx.doi.org/10.3390/ijms21113854
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