Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma
2021 | journal article. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma
Frontzek, F.; Staiger, A. M.; Zapukhlyak, M.; Xu, W.; Bonzheim, I.; Borgmann, V. & Sander, P. et al. (2021)
Nature Communications, 12(1) art. 5183. DOI: https://doi.org/10.1038/s41467-021-25405-w
Documents & Media
Details
- Authors
- Frontzek, Fabian; Staiger, Annette M.; Zapukhlyak, Myroslav; Xu, Wendan; Bonzheim, Irina; Borgmann, Vanessa; Sander, Philip; Baptista, Maria Joao; Heming, Jan-Niklas; Berning, Philipp; Lenz, Georg
- Abstract
- 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.
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. - Issue Date
- 2021
- Journal
- Nature Communications
- eISSN
- 2041-1723
- Language
- English