Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma
Abstract: 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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Nature communications. - 12 (2021) , 5183, ISSN: 2041-1723
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2021
- Creator
- DOI
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10.1038/s41467-021-25405-w
- URN
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urn:nbn:de:bsz:25-freidok-2209952
- Rights
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Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:22 AM CEST
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Associated
- Frontzek, Fabian
- Veratti, Pia
- Ehrenfeld, Sophia
- Miething, Cornelius
- Grau, Michael
- Lenz, Georg
- Universität
Time of origin
- 2021
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