2026-04-17T11:36:05Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1802562025-11-20T14:58:00Zcom_2072_1057col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Frontzek, Fabian author Staiger, Annette M. author Zapukhlyak, Myroslav author Xu, Wendan author Bonzheim, Irina author Borgmann, Vanessa author Sander, Philip author Baptista, Maria Joao author Heming, Jan-Niklas author Berning, Philipp author Wullenkord, Ramona author Erdmann, Tabea author Lutz, Mathias author Veratti, Pia author Ehrenfeld, Sophia author Wienand, Kirsty author Horn, Heike author Goodlad, John R. author Wilson, Matthew R. author Anagnostopoulos, Ioannis author Lamping, Mario author González Barca, Eva author Climent, Fina author Salar, Antonio author Castellvi, Josep author Abrisqueta Costa, Pau author Menarguez, Javier author Aldamiz, Teresa author Richter, Julia author Klapper, Wolfram author Tzankov, Alexandar author Dirnhofer, Stefan author Rosenwald, Andreas author Mate, José L. author Tapia, Gustavo author Lenz, Peter author Miething, Cornelius author Hartmann, Wolfgang author Chapuy, Björn author Fend, Falko author Ott, German author Navarro, José-Tomás author Grau, Michael author Lenz, Georg author 2021-09-27T13:06:54Z 2021-09-27T13:06:54Z 2021-08-31 2021-09-23T09:04:51Z 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. Cèl·lules B Càncer Mapatge cromosòmic humà B cells Cancer Human gene mapping Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma