| Literature DB >> 33447829 |
Ruth Flümann1,2,3,4, Tim Rehkämper1,2,3,4, Pascal Nieper1,2,3,4, Hans Christian Reinhardt5, Gero Knittel1,2,3,4, Pauline Pfeiffer1,2,3,4, Alessandra Holzem1,2,3,4, Sebastian Klein6, Sanil Bhatia7, Moritz Kochanek1,2,3,4, Ilmars Kisis1,2,3,4, Benedikt W Pelzer1,2,3,4, Heinz Ahlert7, Julia Hauer8,9, Alexandra da Palma Guerreiro1,2,4, Jeremy A Ryan10, Maurice Reimann11, Arina Riabinska1,2,3,4, Janica Wiederstein4, Marcus Krüger4, Martina Deckert2,12, Janine Altmüller13, Andreas R Klatt14, Lukas P Frenzel1,2,4, Laura Pasqualucci15, Wendy Béguelin16, Ari M Melnick16, Sandrine Sander17, Manuel Montesinos-Rongen2,12, Anna Brunn2,12, Philipp Lohneis2,3,6, Reinhard Büttner2,3,6, Hamid Kashkar3,4,18, Arndt Borkhardt7, Anthony Letai10, Thorsten Persigehl2,19, Martin Peifer2,3,20, Clemens A Schmitt11,21.
Abstract
Based on gene expression profiles, diffuse large B cell lymphoma (DLBCL) is sub-divided into germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL. Two of the most common genomic aberrations in ABC-DLBCL are mutations in MYD88, as well as BCL2 copy number gains. Here, we employ immune phenotyping, RNA-Seq and whole exome sequencing to characterize a Myd88 and Bcl2-driven mouse model of ABC-DLBCL. We show that this model resembles features of human ABC-DLBCL. We further demonstrate an actionable dependence of our murine ABC-DLBCL model on BCL2. This BCL2 dependence was also detectable in human ABC-DLBCL cell lines. Moreover, human ABC-DLBCLs displayed increased PD-L1 expression, compared to GCB-DLBCL. In vivo experiments in our ABC-DLBCL model showed that combined venetoclax and RMP1-14 significantly increased the overall survival of lymphoma bearing animals, indicating that this combination may be a viable option for selected human ABC-DLBCL cases harboring MYD88 and BCL2 aberrations.Entities:
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Year: 2021 PMID： 33447829 PMCID： PMC7806186 DOI： 10.1158/2643-3230.BCD-19-0059
Source DB: PubMed Journal: Blood Cancer Discov ISSN： 2643-3230