Gene expression derived from alternative promoters improves prognostic stratification in multiple myeloma
Year: 2021
Type: article
Abstract: Clinical and genetic risk factors are currently used in multiple myeloma (MM) to stratify patients and to design specific therapies. However, these systems do not capture the heterogeneity of the disease supporting the development of new prognostic factors. In this study, we identified active promoters and alternative active promoters in 6 different B cell subpopulations, including bone-marrow plasma cells, and 32 MM patient samples, using RNA-seq data. We find that expression initiated at both regular and alternative promoters was specific of each B cell subpopulation or MM plasma cells, showing a remarkable level of consistency with chromatin-based promoter definition. Interestingly, using 595 MM patient samples from the CoMMpass dataset, we observed that the expression derived from some alternative promoters was associated with lower progression-free and overall survival in MM patients independently of genetic alterations. Altogether, our results define cancer-specific alternative active promoters as new transcriptomic features that can provide a new avenue for prognostic stratification possibilities in patients with MM.
Source: Leukemia
Institutions: Centro de Investigación Médica Aplicada, Universidad de Navarra, Centro de Investigación Biomédica en Red de Cáncer, Fundació Clínic per a la Recerca Biomèdica, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Weill Cornell Medicine, Clinica Universidad de Navarra, Institució Catalana de Recerca i Estudis Avançats, Universitat de Barcelona
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
Funders: Multiple Myeloma Research Foundation, International Myeloma Foundation, Fundación Ramón Areces, Fundació la Marató de TV3, Ministerio de Ciencia, Innovación y Universidades, Cancer Research UK, Fonds National de la Recherche Luxembourg, Associazione Italiana per la Ricerca sul Cancro, Centro de Investigación Biomédica en Red de Cáncer, Gobierno de Navarra, Qatar National Research Fund, Instituto de Salud Carlos III
Awards: G1061961021, G1075404386, G1278828043, G2370590264, G2559588348, G2593314801, lncRNAs: nuevas dianas para el tratamiento del mieloma múltiple mediante quimeras aptamero-siRNAs., G36935394, Detección y validación funcional de los RNAs largos no codificantes específicos de la célula plasmática en el Mieloma Múltiple, G4784474418, G5243743885, G5948419412, G6368058359, G690406048, G6925679483, Estudio de la arquitectura genómica y transcripcional en SMDs como herramienta para la determinación de factores pronósticos y nuevas dianas terapéuticas, G7455154710, G8148640433, G8325309054
OpenAlex ID: W3162818840