结外播散是侵袭性B细胞淋巴瘤的重要特征。由于缺乏可用的动物模型,关于淋巴瘤结外播散的研究非常有限。这里,我们发现了一种新的细胞系,名叫MA-K,起源于Eμ-Myc;Cdkn2a-/-细胞系,在这项研究中命名为MA-LN。与MA-LN相比,在淋巴瘤移植模型中,MA-K倾向于在肾脏而不是淋巴结中传播,类似于人类原发性肾淋巴瘤。转录组分析显示MA-K在培养过程中经历了转录进化。我们在这项研究中提出的专门的转录模式分析确定FOXO1-BTG1-MYD88模式是在MA-K中形成的。进一步分析发现,翻译途径是MA-K中特别表达基因(SEGs)中最富集的途径。在SEGs中,三个上调的基因,RPLP2,RPS16和MRPS16,以及五个下调基因,SSPN,MA-K中的CD52、ANKRD37、CCDC82和VPREB3被鉴定为预测人DLBCL的临床结果的有希望的生物标志物。此外,5个基因标记的联合表达可以有效预测3组中人类DLBCL的临床结局.这些发现表明MA-K细胞系与人类侵袭性B细胞淋巴瘤具有很强的临床相关性。此外,MA-K原发性肾淋巴瘤模型,作为一种新的同基因小鼠模型,对于淋巴瘤播散的基础研究以及化疗和免疫治疗的临床前疗效评估都将非常有用。
Extranodal dissemination is an important feature of aggressive B-cell lymphoma. Owing to the lack of available animal models, the study on extranodal dissemination of lymphoma is greatly limited. Here, we identified a novel cell line, named MA-K, which originated from the Eμ-Myc;Cdkn2a-/- cell line, named MA-LN in this study. Compared to MA-LN, MA-K tended to disseminate in the kidney rather than the lymph nodes in the lymphoma transplantation model, resembling human primary renal lymphoma. The transcriptome analysis revealed that MA-K had undergone transcriptional evolution during the culture. The specialized transcriptional pattern analysis we proposed in this study identified that the FOXO1-BTG1-MYD88 pattern was formed in MA-K. Further analysis found that the translation pathway was the most enriched pathway in specially expressed genes (SEGs) in MA-K. Among the SEGs, three upregulated genes, RPLP2, RPS16, and MRPS16, and five downregulated genes, SSPN, CD52, ANKRD37, CCDC82, and VPREB3, in MA-K were identified as promising biomarkers to predict the clinical outcomes of human DLBCL. Moreover, the joint expression of the five-gene signature could effectively predict clinical outcomes of human DLBCL in three groups. These findings suggested that the MA-K cell line had strong clinical relevance with human aggressive B-cell lymphoma. Moreover, the MA-K primary renal lymphoma model, as a novel syngenetic mouse model, will be greatly useful for both basic research on lymphoma dissemination and preclinical efficacy evaluation of chemotherapy and immunotherapy.