(2) Li Xiaoxi; Deng Minyao; Zhang Chenxiao; Luo Lingli; Qian Hui ; Establishment of a primary renal lymphoma model and its clinical relevance, Frontiers in Oncology, 2023, 13:1089187

Abstract: Extranodal dissemination is an important feature of aggressive B-cell lymphoma. Due 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 lymph nodes in lymphoma transplantation model, resembling human primary renal lymphoma. The transcriptome analysis revealed that MA-K had undergone the transcriptional evolution during the culture. Specialized transcriptional pattern analysis, we proposed in this study, identified that FOXO1-BTG1-MYD88 pattern was formed in MA-K. Further analysis found that translation pathway was the most enriched pathway in specially expressed genes (SEGs) in MA-K. Among the SEGs, 3 up-regulated genes, RPLP2, RPS16 and MRPS16, and 5 down-regulated 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 5-gene signature could effectively predict clinical outcomes of human DLBCL in triple 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 the basic research on lymphoma dissemination and preclinical efficacy evaluation of chemotherapy and immunotherapy.

(1) Li Xiaoxi; Jiang Yong; Qian Hui ; Lymphoma dissemination is a pathological hallmark for malignant progression of B-cell lymphoma, Frontiers in Immunology, 2023, 14:1286411

Abstract: Extranodal lymphoma occurs in one-third of lymphoma patients and is a key indicator of the international prognostic index, associated with unfavorable outcomes. Due to the lack of ideal models, the causes and characteristics of extranodal lymphoma are greatly underexplored. Recently, we observed a high incidence of extranodal lymphoma in two types of mouse models with tropism for the brain and kidneys. These findings prompt us to rethink the pathological progression of lymphoma colonization in lymph nodes and non-lymphoid organs. Nodal lymphoma, primary extranodal lymphoma and secondary extranodal lymphoma should be biologically and clinically distinctive scenarios. Based on the observations in mouse models with extranodal lymphoma, we propose that lymphoma dissemination can be seen as lymphoma losing the ability to home to lymph nodes. The pathological process of nodal lymphoma should be referred to as lymphoma homing to distinguish it from benign hyperplasia. Lymphoma dissemination, defined as a pathological process that lymphoma can occur in almost any part of the body, is a key pathological hallmark for malignant progression of B-cell lymphoma. Reshaping cellular plasticity is a promising strategy to allow transformed cells to homing back to lymph nodes and re-sensitize tumor cells to treatment. From this perspective, we provide new insights into the pathological progression of lymphoma dissemination and its inspiration on therapeutic interventions. We believe that establishing extranodal lymphoma mouse models, identifying molecular mechanism governing lymphoma dissemination, and developing therapies to prevent lymphoma dissemination will become emerging topics for fighting relapsed and refractory lymphoma.