2026-04-14T03:33:55Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/1802562025-11-20T14:58:00Zcom_2072_1057col_2072_478916col_2072_478917
urn:hdl:2445/180256
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma
Frontzek, Fabian
Staiger, Annette M.
Zapukhlyak, Myroslav
Xu, Wendan
Bonzheim, Irina
Borgmann, Vanessa
Sander, Philip
Baptista, Maria Joao
Heming, Jan-Niklas
Berning, Philipp
Wullenkord, Ramona
Erdmann, Tabea
Lutz, Mathias
Veratti, Pia
Ehrenfeld, Sophia
Wienand, Kirsty
Horn, Heike
Goodlad, John R.
Wilson, Matthew R.
Anagnostopoulos, Ioannis
Lamping, Mario
González Barca, Eva
Climent, Fina
Salar, Antonio
Castellvi, Josep
Abrisqueta Costa, Pau
Menarguez, Javier
Aldamiz, Teresa
Richter, Julia
Klapper, Wolfram
Tzankov, Alexandar
Dirnhofer, Stefan
Rosenwald, Andreas
Mate, José L.
Tapia, Gustavo
Lenz, Peter
Miething, Cornelius
Hartmann, Wolfgang
Chapuy, Björn
Fend, Falko
Ott, German
Navarro, José-Tomás
Grau, Michael
Lenz, Georg
Cèl·lules B
Càncer
Mapatge cromosòmic humà
B cells
Cancer
Human gene mapping
Plasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients.
2021-09-27T13:06:54Z
2021-09-27T13:06:54Z
2021-08-31
2021-09-23T09:04:51Z
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Reproducció del document publicat a: https://doi.org/10.1038/s41467-021-25405-w
Nature Communications, 2021, vol. 12, num. 1
https://doi.org/10.1038/s41467-021-25405-w
cc by (c) Frontzek, Fabian et al, 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
Springer Science and Business Media LLC
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))