Detalle Publicación

Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma

Autores: Ordóñez Ciriza, Raquel; Kulis, M.; Russiñol, N.; Chapaprieta, V.; Carrasco-León, A.; García-Torre, B.; Charalampopoulous, S.; Clot, G.; Beekman, R.; Meydan, C.; Duran-Ferrer, M.; Verdaguer-Dot, N.; Vilarrasa-Balsi, R.; Soler-Vila, P.; Garate Iturriagagoitia, Leire; Miranda, E.; San José Enériz, Edurne; Rodríguez Madoz, Juan Roberto; Ezponda Itoiz, Teresa; Martínez Turrillas, Rebeca; Vilas Zornoza, Amaia; LARA ASTIASO, David; Dupéré-Richer, D.; Martens, J. A. H.; El-Omri, H.; Taha, R. Y.; Calasanz Abinzano, María José; Paiva, Bruno; San Miguel Izquierdo, Jesús; Flicek, P.; Gut, I.; Melnick, A.; Mitsiades, C. S.; Licht, J. D.; Campo, E.; Stunnenberg, H. G.; Aguirre Ena, Xabier (Autor de correspondencia); Prosper Cardoso, Felipe (Autor de correspondencia); Martín-Subero, J. I. (Autor de correspondencia)
Título de la revista: GENOME RESEARCH
ISSN: 1088-9051
Volumen: 30
Número: 9
Páginas: 1217 - 1227
Fecha de publicación: 2020
Multiple myeloma (MM) is a plasma cell neoplasm associated with a broad variety of genetic lesions. In spite of this genetic heterogeneity, MMs share a characteristic malignant phenotype whose underlying molecular basis remains poorly characterized. In the present study, we examined plasma cells from MM using a multi-epigenomics approach and demonstrated that, when compared to normal B cells, malignant plasma cells showed an extensive activation of regulatory elements, in part affecting coregulated adjacent genes. Among target genes up-regulated by this process, we found members of the NOTCH, NF-kB, MTOR signaling, and TP53 signaling pathways. Other activated genes included sets involved in osteoblast differentiation and response to oxidative stress, all of which have been shown to be associated with the MM phenotype and clinical behavior. We functionally characterized MM-specific active distant enhancers controlling the expression of thioredoxin (TXN), a major regulator of cellular redox status and, in addition, identified PRDM5 as a novel essential gene for MM. Collectively, our data indicate that aberrant chromatin activation is a unifying feature underlying the malignant plasma cell phenotype.