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Int J Mol Sci ; 21(11)2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32481768

RESUMO

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.


Assuntos
Regulação Neoplásica da Expressão Gênica , Impressão Genômica , Células-Tronco Mesenquimais/metabolismo , Mieloma Múltiplo/metabolismo , Transcriptoma , Adipogenia , Idoso , Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Diferenciação Celular , Técnicas de Cocultura , Resistencia a Medicamentos Antineoplásicos , Feminino , Perfilação da Expressão Gênica , Humanos , Imunossupressores/farmacologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia , Análise de Componente Principal , Recidiva , Linfócitos T/citologia
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