MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies

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Abstract
MUM1/IRF4 is a myeloma-associated oncogene transcriptionally activated as a result of t(6;14)(p25,q32) chromosomal translocation and by virtue of its juxtaposition to the immunoglobulin heavy chain gene (IgH) locus. When this oncogene becomes non-functional, no activated B/T lymphocytes and Ig secreting plasma cells are observed, suggesting that MUM1/IRF4 is crucial for lymphoid development. Its expression was analyzed in both reactive lymphoid and lymphoma tissues by means of an immunohistochemical technique using specific goat antiserum against MUM1/IRF4. This analysis detected a 50 kDa MUM1product whose localization was restricted to the nuclei of the lymphocytes. The MUM1+ cells in reactive lymph nodes were found to consist of plasma cells and a small fraction (approximately 7.9%) of B cells harboring CD20+CD38+, which were located in the light zone of the germinal center. MUM1 expression in peripheral blood B/T lymphocytes was upregulated by mitogenic stimuli, suggesting that MUM1 positivity represents the activated state of the B/T cells. In B cell non-Hodgkin's lymphoma (NHL), MUM1 expression was observed in 73.2% (30/41) of diffuse large B cell lymphoma (DLBCL), 20% (1/5) of marginal zone lymphoma (MZL) and 43% (3/7) of small lymphocytic lymphoma (SLL) cases, whereas it was not seen in any cases of mantle cell lymphoma (MCL) or follicle center lymphoma (FCL). Also, MUM1 was stained at high intensity in various types of T cell lymphomas including adult T cell leukemia/lymphoma (ATL/L) and anaplastic large cell lymphoma (ALCL) and in the majority of Hodgkin's diseases. Our results suggest that a major proportion of lymphomas comprise either physiologically or aberrantly activated neoplastic lymphocytes expressing the MUM1 protein.