Review Article: A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgin Lymphoma in Ganp-Transgenic Mice 

The main idea of the article is Ig-ganpTg was the first cytological model of Hodgin Lymphoma (HL). This article is also about GANP is immunocytochemically expressed on human HRS cells and may regulate cell transdifferentiation of B cells to macrophages using ganp-transgenic mice under the control of Ig promoter and intron enhancer Eµ (Ig-ganpTg mice). Ig-ganpTg mice spontaneously develop Hodginoid lymphomas, which have similar properties as B-cell/macrophage biphenotypic cells such as phagocytic activity and macrophage-derived cytokine secretion also the idea of this article. 

The first finding of the article is the overexpressed GANP on HRS cells and that overexpressed may be associated with Hodgin lymphomagenesis. This investigation was using immunocytochemistry in human HL cell lines HD70 and L428. HD70 and L428 cell lines indicated a strong expression of GANP. This overexpressed the same as in CD15 and CD30 which is a marker of HL. 

Another finding of this article is GANP may not influence early B-cell differentiation. In this article showed that GANP may contribute to late-stage B-cell development in a Lyn-dependent manner, but GANP regulates cell transdifferentiation between B cells and macrophages in a Lyn-independent manner. Different signaling through the Lyn-mediated pathway to PU.1-binding sites of the promoter regions in various regulatory molecules may not cause a drastic change in fetal and adult hematopoietic precursor cell differentiation in the liver and bone marrow; however, it may alter germinal center B-cell differentiation in the peripheral lymphoid organs in the humoral immune-deficient state. This article also demonstrated that malignant lymphomas obtained from Ig-ganpTg mice have biphenotypic characteristics of B cells/macrophages and mimic human HL. 

Phagocytosis assay using fluorescent microspheres indicated high phagocytic activity of B/M-2 cells and that B/M-2 cells show the functionality of macrophages. As we know that, B cells and macrophages can be principally determined based on the expressions of specific markers, such as CD45R (B220), CD19, and Ig proteins are B-cell lineage markers (CD11b, CD13, CD15, F4/80, CD68, and CD204) are macrophage lineage markers. B-cell lineage differentiation is committed with the expression of the transcripts of Pax5, mb-1, IL-7R, RAG1, and RAG2. This proceeds to Ig gene rearrangements, leading to the production of IgM and IgD. Then, macrophages are ultimately distinguished by their phagocytic activity and secretion of various inflammatory cytokines. The lymphoma cells derived from Ig-ganpTg mice showed both Ig-gene rearrangements and phagocytic activity, these were characterized as B-cell/macrophage biphenotypic cells with close resemblance to human HL. In the last finding, this article showed a cytological model of HL as the first cytological model of HL. 

This finding has many contributions to the disease in which Hodgin Lymphoma (HL). This finding may add an understanding of HL properties. Novel cytological model for HL may help another study about cytopathological etiology and lymphomagenesis of HL. With understanding about cytopathological etiology and lymphomagenesis of HL, many researchers could make some new targets for chemotherapy or radiotherapy for this disease. This finding also could make a new understanding of how to prevent this malignancy in population. This article also said that GANP is known to operate downstream of CD40. Thus, the upstream or downstream molecules of GANP may be alternative therapeutic targets of HL and CD30. With this result, researchers may custom drugs or molecules with this understanding to target HL. 

The cause of Hodgkin Lymphoma is unknown, but genetic susceptibility and environmental associations (eg, occupation, such as woodworking; the history of treatment with phenytoin, radiation therapy, or chemotherapy; infection with Epstein-Barr virus, Mycobacterium tuberculosis, herpesvirus type 6, HIV) play a role. Risk is slightly increased in people with certain types of immunosuppression (eg, posttransplant patients taking immunosuppressants); in people with congenital immunodeficiency disorders (ataxia-telangiectasia, Klinefelter syndrome, Chediak-Higashi syndrome, Wiskott-Aldrich syndrome), and people with certain autoimmune disorders (rheumatoid arthritis, celiac sprue, Sjogren syndrome, systemic lupus erythematosus). This novel cytopathological property maybe can not be suited for all possible causes that have a role in the development of HL. 

Cytopathological molecular analysis of this type of cancer still challenging because there is no murine model before. But, this new model needs more another study to understanding and reproduce this kind of model. If this can be reproduced, this might help future investigation about cytopathological etiology and oncogenesis of HL, also about targeted genetic drug therapy to this type of malignancy.