IRF4 expression without IRF4 rearrangement is a general feature of primary cutaneous diffuse large B-cell lymphoma, leg type.

摘要

The involvement of the interferon regulatory factor 4 gene (IRF4), also known as multiple myeloma antigen 1 (MUM1), in balanced rearrangement or translocation has been recently observed in a subset of cutaneous T-cell lymphomas (CTCLs), such as cutaneous anaplastic large-cell lymphoma (C-ALCL) and transformed mycosis fungoides (Feldman et al., 2009; Pham-Ledard et al., 2009). IRF4 expression reaches a high level in differentiated plasma cells and is also detectable by immunostaining in some activated T cells and melano-cytes, with the latter providing internal positive controls on skin sections (Falini et al., 2000; Lu, 2008). Despite such a restricted immunostaining pattern, IRF4 is an essential regulator at multiple steps of B-cell differentiation, such as pre-B- cell differentiation, germinal center formation, immunoglobulin class switch recombination, and terminal differentiation of B cells to plasma cells, as shown in IRF4-deficient mice (reviewed in Shaffer et al., 2009). IRF4 is also essential for T-helper (Th) cell differentiation and is required for either Th2 or Th17 cell development (Brustle et al., 2007; Zheng et al., 2009). An oncogenic role of IRF4 has first been supported by the identification of IRF4 involvement in the t(6;14)(p25;q32) translocation in some cases of multiple myeloma (MM) (lida etal., 1997). In t(6;14)(p25;q32), IRF4 is juxtaposed with the immunoglobulin heavy-chain gene locus leading to IRF4 deregulated expression (lida et al., 1997; Yoshida etal., 1999; Shaffer et al., 2008). Alternatively, IRF4 rearrangements in peripheral T-cell lymphoma do not commonly involve either the TCRB or the TCRA gene locus, as shown in eight C-ALCL and two systemic T-cell lymphomas (Feldman et al., 2009).