Bergsagel Peter Leif, Chesi Marta
Department of Medicine, Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, AZ 85259.
Department of Medicine, Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, AZ 85259.
Semin Hematol. 2025 Feb;62(1):50-57. doi: 10.1053/j.seminhematol.2024.11.003. Epub 2024 Nov 16.
Immunocompetent murine models of multiple myeloma are critical for understanding the pathogenesis of multiple myeloma and for the development of novel immunotherapeutics. Different models are available in Balb/c and C57Bl strains, each with different advantages and disadvantages. The availability of many transplantable cell lines allows for the conduct of experiments with large cohorts of mice bearing identical tumors, while cell lines that grow in vitro can be used for genetic manipulations. The introduction of human CRBN into these models allows for the study of IMiDs and cereblon based PROTACs in mice. New genetically engineered models based on germinal center cell activation of Nsd2 or Ccnd1 together with constitutive NFkB are being developed to model some of the important genetic subtypes of human multiple myeloma.
具有免疫活性的多发性骨髓瘤小鼠模型对于理解多发性骨髓瘤的发病机制以及新型免疫疗法的开发至关重要。在Balb/c和C57Bl品系中有不同的模型,每个模型都有不同的优缺点。许多可移植细胞系的存在使得能够对大量携带相同肿瘤的小鼠进行实验,而体外生长的细胞系可用于基因操作。将人类CRBN引入这些模型能够在小鼠中研究免疫调节药物(IMiDs)和基于脑啡肽的蛋白水解靶向嵌合体(PROTACs)。基于Nsd2或Ccnd1的生发中心细胞激活以及组成型核因子-κB(NFkB)的新型基因工程模型正在开发中,以模拟人类多发性骨髓瘤的一些重要基因亚型。