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Based on gene expression profiles, diffuse large B-cell lymphoma (DLBCL) is subdivided 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 sequencing, and wholeexome 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 with GCB-DLBCL. In vivo experiments in our ABC-DLBCL model showed that combined venetoclax and PD-1 blockade 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.SignificAnce: Oncogenic Myd88 and BCL2 cooperate in murine DLBCL lymphomagenesis. The resulting lymphomas display morphologic and transcriptomic features reminiscent of human ABC-DLBCL. Data derived from our Myd88/BCL2-driven autochthonous model demonstrate that combined BCL2 and PD-1 blockade displays substantial preclinical antilymphoma activity, providing preclinical proofof-concept data, which pave the way for clinical translation.

Vaccination is one of the most useful preventive interventions in healthcare. The purpose of our study was to gain overview of the opinions, knowledge, and engagement in vaccination practices among medical students (MS) and junior doctors (JD) in Europe. The survey was distributed from March 2016 until August 2016 via the e-mail and social media of the European Medical Students’ Association. In total, 1821 responses from MS and JD from 34 countries in the European region were analysed. The majority of respondents agreed that vaccines are useful (98.7%) and effective (97.2%). Although the necessity of revaccination was supported by 99.2%, only 68.0% of the respondents went through with it. Even though the potential benefit of the flu vaccination seems to be acknowledged by our participants, only 22.1% of MS and JD declared getting the flu shot every or every other season. MS and JD were in favour of specific mandatory vaccination for medical staff (86.0%) and medical students (82.7%). Furthermore, we analysed the self-reported vaccination coverage of our participants regarding 19 vaccines. Of the respondents, 89.5% claimed to provide advice about vaccination to their friends and family. In conclusion, European MS and JD have a very positive attitude towards vaccination. However, their behaviour and knowledge demonstrate certain gaps which should be further addressed in medical education.