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oai:gredos.usal.es:10366/1407912026-02-19T09:49:45Zcom_10366_4577com_10366_4576com_10366_3823com_10366_133043col_10366_4578col_10366_135272

Paiva, Bruno Puig Morón, Noemí Cedena, Teresa de Jong, B G Ruiz, Y Rapado, Inmaculada Martinez-Lopez, Joaquin Cordón, Lourdes Alignani, D Delgado Notario, Juan Antonio van Zelm, M C van Dongen, Jacques J. M. Pascual, M Agirre, X Prósper, Felipe Martín-Subero, J I Vidriales Vicente, María Belén Gutiérrez Gutiérrez, Norma Carmen Hernandez, M T Oriol, Albert Echeveste, María-Asunción Gonzalez, Y Johnson, S K Epstein, J Barlogie, B Morgan, Gareth J. Orfao de Matos Correia e Vale, José Alberto Bladé, Joan Mateos Manteca, María Victoria Lahuerta, Juan-Jose San Miguel, Jesús F 2016 [EN] The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n = 20) that the CD19 − CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19 − CD81+ and CD19 − CD81 − BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19 − CD81 −) clones, 38% intermediate-differentiated (CD19 − CD81+) and 3% less-differentiated (CD19+CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression-free (HR: 1.7; P = 0.005) and overall survival (HR: 2.1; P = 0.006). Longitudinal comparison of diagnostic vs minimal-residual-disease samples (n = 40) unraveled that in 20% of patients, less-differentiated PCs subclones become enriched after therapy-induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less-differentiated clonal PCs retain high expression of genes related to preceding B-cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less-differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles. http://hdl.handle.net/10366/140791 eng Differentiation stage of myeloma plasma cells: biological and clinical significance info:eu-repo/semantics/article TEXT Gredos. Repositorio Documental de la Universidad de Salamanca Hispana