Detalle Publicación

Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development

Autores: Alameda Serrano, Daniel; Goicoechea Oroz, Ibai; Vicari, M.; Arriazu Ruiz, Elena; Nevone, A.; Rodríguez Díaz, Saray; Lasa Ventura, Marta; Puig, N.; Cedena, M. T.; Alignani, Diego Oscar; Garate Luzuriaga, Sonia; LARA ASTIASO, David; Vilas Zornoza, Amaia; Sarvide Plano, Sarai; Ocio, E. M.; Lecumberri Villamediana, Ramón; García de Coca, A.; Labrador, J.; González, M. E.; Palomera, L.; Gironella, M.; Cabañas, V.; Casanova, M.; Oriol, A.; Krsnik, I.; Pérez-Montaña, A.; de la Rubia, J.; de la Puerta, J. E.; de Arriba, F.; Michele Fazio, V.; Martínez-López, J.; Lahuerta, J. J.; Mateos, M. V.; Odero, María D.; Prosper Cardoso, Felipe; Weiner, A.; Amit, I.; Nuvolone, M.; San Miguel Izquierdo, Jesús; Paiva, Bruno (Autor de correspondencia)
Título de la revista: BLOOD
ISSN: 0006-4971
Volumen: 138
Número: 17
Páginas: 1583 - 1589
Fecha de publicación: 2021
Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, but there are no studies investigating the differentiation stage of tumor PCs in patients with AL and MM. We sought to define a transcriptional atlas of normal PC development (n=11) in secondary lymphoid organs (SLO), peripheral blood (PB) and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL (n=37), MM (n=46) and MGUS (n=6). Based on bulk and single-cell RNAseq, we observed thirteen TPs during transition of normal PCs throughout SLO, PB and BM; that CD39 outperforms CD19 to discriminate new-born from long-lived BM-PCs; that tumor PCs expressed the most advantageous TPs of normal PC differentiation; that AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and new-born BM-PCs; that AL and MM patients enriched in immature TPs had inferior survival; and that TPs related with protein N-linked glycosylation are upregulated in AL. Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies.