Ferrad Melissa, Ghazzaui Nour, Issaoui Hussein, Drouineau Emilie, Oblet Christelle, Marchiol Tiffany, Cook-Moreau Jeanne, Denizot Yves
UMR CNRS 7276, INSERM U1262, Equipe Labellisée LIGUE 2018, Université de Limoges, Limoges, France.
I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Leuk Lymphoma. 2022 Sep;63(9):2114-2125. doi: 10.1080/10428194.2022.2064989. Epub 2022 Apr 28.
The 3' regulatory region (3'RR) located downstream from the Cα gene is the conductor of transcription, accessibility, and remodeling of the IgH locus at mature B-cell stages. Convincing demonstrations of the essential contributions of the 3'RR in B-cell lymphomagenesis have been provided by mouse models which bring the oncogene under the 3'RR transcriptional control. In this study, we developed a mouse model of CD138 plasma B-cell lymphomas. If the KI of directly into Cα just 5' to the 3'RR in iMycCα mice produced B-cell lymphomas with low kinetics, we enforced production in iMycCα mice by the generation of homozygous transgenic mice. Our results show that homozygous iMycCα mice lead to a mouse model of plasma CD138 B-cell lymphomas with interesting and wide transcriptomic similarities to human multiple myeloma and appropriated emergence kinetics that can be used to test new experimental therapeutic approaches.
位于Cα基因下游的3'调控区（3'RR）是成熟B细胞阶段IgH基因座转录、可及性和重塑的指挥者。将癌基因置于3'RR转录控制之下的小鼠模型有力地证明了3'RR在B细胞淋巴瘤发生中的重要作用。在本研究中，我们构建了CD138浆细胞B细胞淋巴瘤的小鼠模型。如果在iMycCα小鼠中直接将 插入到紧挨着3'RR 5'端的Cα中所产生的KI导致B细胞淋巴瘤的发生动力学较慢，我们通过生成纯合转基因小鼠来增强iMycCα小鼠中的 产生。我们的结果表明，纯合iMycCα小鼠导致了一种浆细胞CD138 B细胞淋巴瘤的小鼠模型，该模型与人类多发性骨髓瘤具有有趣且广泛的转录组相似性，以及合适的出现动力学，可用于测试新的实验性治疗方法。
