RT Journal
A1 Ordoñez, Raquel
A1 Kulis, Marta
A1 Russiñol, Nuria
A1 Chapaprieta, Vicente
A1 Carrasco-Leon, Arantxa
A1 García-Torre, Beatriz
A1 Charalampopoulou, Stella
A1 Clot, Guillem
A1 Beekman, Renée
A1 Meydan, Cem
A1 Duran-Ferrer, Martí
A1 Verdaguer-Dot, Núria
A1 Vilarrasa-Blasi, Roser
A1 Soler-Vila, Paula
A1 Garate, Leire
A1 Miranda, Estíbaliz
A1 San José-Enériz, Edurne
A1 Rodriguez-Madoz, Juan R.
A1 Ezponda, Teresa
A1 Martínez-Turrilas, Rebeca
A1 Vilas-Zornoza, Amaia
A1 Lara-Astiaso, David
A1 Dupéré-Richer, Daphné
A1 Martens, Joost H.A.
A1 El-Omri, Halima
A1 Taha, Ruba Y.
A1 Calasanz, Maria J.
A1 Paiva, Bruno
A1 San Miguel, Jesus
A1 Flicek, Paul
A1 Gut, Ivo
A1 Melnick, Ari
A1 Mitsiades, Constantine S.
A1 Licht, Jonathan D.
A1 Campo, Elias
A1 Stunnenberg, Hendrik G.
A1 Agirre, Xabier
A1 Prosper, Felipe
A1 Martin-Subero, Jose I.
T1 Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma
JF Genome Research 
JO Genome Research 
YR 2020 
FD September 01 
VO 30 
IS 9 
SP 1217 
OP 1227 
DO 10.1101/gr.265520.120 
UL http://genome.cshlp.org/content/30/9/1217.abstract 
AB 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.