However, ectopic IRF4 expression can augment EBV lytic gene expression induced by anti-immunoglobulin (anti-Ig) or sodium butyrate treatment in all tested lymphoma cells, whereas IRF4 knockout in Raji cells, the only BL cell line with detectable endogenous IRF4 expression, abolishes EBV lytic gene expression induced by anti-Ig, and this is accompanied by the reduction of Blimp-1 expression, whose overexpression, in turn, can rescue EBV lytic gene expression in IRF4 knockout Raji cells.
Using high throughput expression profiling, we have previously identified LIMD1 as a common marker associated with the oncogenic transcription factor IRF4 in EBV-related lymphomas and other hematological malignancies.
The pediatric group included Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and MUM1-positive-lymphoma in 7, 3 and 2 cases, respectively.
Our report highlights the clinicopathologic features of IFR4/MUM1-positive lymphoma in WR with co-expression of CD5 and CD10, and thereby provides insight into this newly recognized disease entity.
The Interferon Regulatory Factor 4 (IRF4) gene encodes a transcription factor important for key developmental stages of hematopoiesis, with known oncogenic implications in multiple myeloma, adult leukemias and lymphomas.
With the exception of pediatric follicular lymphoma with IRF4-translocation, the genetic events associated with these lymphomas have not yet been defined.
The cases were classified according to the 2008 World Health Organization classification criteria, with application of immunohistochemistry for the detection of CD10, BCL-6, and MUM1 proteins to divide the lymphomas into germinal center and nongerminal center types.
Our results suggest that a major proportion of lymphomas comprise either physiologically or aberrantly activated neoplastic lymphocytes expressing the MUM1 protein.