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Establishment of a primary renal lymphoma model and its clinical relevance.

ABSTRACT: 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.

SUBMITTER: Li X

PROVIDER: S-EPMC10493870 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Establishment of a primary renal lymphoma model and its clinical relevance.

Li Xiaoxi X Deng Minyao M Zhang Chenxiao C Luo Lingli L Qian Hui H

Frontiers in oncology 20230828

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<sup>-/-</sup> 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 lym ...[more]

PMID: 37700827

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Project description:Background: Studies recently support that non-HLA antigens could be additional targets of injury in organ transplant recipients, and MICA was associated with an increased risk of graft loss. Methods: A ProtoArray platform was used to study 37 serum samples from 22 unique patients (15 renal recipients and 7 healthy controls). Thirty paired pre- and post-transplant serum samples were analyzed for detection of de novo post-transplant antibody responses in the 15 patients (10 acute rejection (AR), 5 Stable). Probes on ProtoArray and cDNA platforms (GSE: 3931) were re-annotated and compartment specific gene lists were analyzed using the integrated genomics method. Normal and transplant kidney IHC were performed for MICA antigen localization. Results: Mean MICA-Ab (antibody) signal intensity was significantly higher in transplant patients compared with healthy controls and de novo MICA-Ab were detected in 73% transplant patients. The mean post-transplant signal intensity of MICA-Ab was the highest in C4d+AR. Detection of MICA-Ab responses did not correlate with time post-transplantation, but significantly correlated with decline in graft function over the subsequent year. Integrative genomics predicted localization of the MICA antigen to the glomerulus. IHC confirmed cytoplasmic MICA staining solely in glomerular podocytes in normal kidney. In the transplant kidney, infiltrating mononuclear lymphocytes (T, B and NK) in AR had additional MICA staining. Conclusions: MICA can be highly detected regardless of graft dysfunction or AR. The intensity signal of the MICA antibody correlates with subsequent decline in graft function. The MICA antigen localizes to the glomerulus and infiltrating mononuclear cells in AR. Pre- and post-transplant serum antibodies were profiled for each patient, using the Invitrogen ProtoArrayÂ® Human Protein Microarray v3.0 platform (Invitrogen, Carlsbad, CA). This platform contains 5,056 non-redundant human proteins expressed in a baculovirus system, purified from insect cells and printed in duplicate onto a nitrocellulose-coated glass slide. Each protein is spotted twice on each array, to measure the quality of the signal intensity. Details for experiment processing and analysis follow the previous publication from our group (13). Prospector software was used to retrieve the expression based on immune response profiling of the .gal files.

Dataset Information

Establishment of a primary renal lymphoma model and its clinical relevance.

Publications

Establishment of a primary renal lymphoma model and its clinical relevance.

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