Mouse models of diffuse large B cell lymphoma

Front Immunol. 2023 Dec 6:14:1313371. doi: 10.3389/fimmu.2023.1313371. eCollection 2023.

Abstract

Diffuse large B cell lymphoma (DLBCL) is a genetically highly heterogeneous disease. Yet, to date, the vast majority of patients receive standardized frontline chemo-immune-therapy consisting of an anthracycline backbone. Using these regimens, approximately 65% of patients can be cured, whereas the remaining 35% of patients will face relapsed or refractory disease, which, even in the era of CAR-T cells, is difficult to treat. To systematically tackle this high medical need, it is important to design, generate and deploy suitable in vivo model systems that capture disease biology, heterogeneity and drug response. Recently published, large comprehensive genomic characterization studies, which defined molecular sub-groups of DLBCL, provide an ideal framework for the generation of autochthonous mouse models, as well as an ideal benchmark for cell line-derived or patient-derived mouse models of DLBCL. Here we discuss the current state of the art in the field of mouse modelling of human DLBCL, with a particular focus on disease biology and genetically defined molecular vulnerabilities, as well as potential targeting strategies.

Keywords: animal models; diffuse large B cell lymphoma (DLBCL); genetically engineered (GE) animals; lymphoma; mouse models.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / therapy
  • Mice

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded through the Deutsche Forschungsgemeinschaft (RE 2246/13-1, SFB 1399/1 2019, SFB 1430/1 2021, SFB 1530/1 2022 to HCR), the Else Kröner-Fresenius Stiftung (EKFS-2014-A06 to HCR, 2016_Kolleg.19 to HCR, RJ), the Deutsche Krebshilfe (70115679, 1117240 and 70113041 to HCR) and a Mildred Scheel Nachwuchszentrum Grant (Grant number 70113307), the German Ministry of Education and Research (BMBF e:Med 01ZX1303A to HCR), the consortium HiRisk-HiGain ERAPERMED 2020-090 (01KU2104), the MERCUR Foundation (IGNITE consortium, Ex-2021-0033), as well as the NRW Network consortium CANTAR (NW21-062B).