IRF4/MUM1 expression is associated with poor survival outcomes in patients with peripheral T-cell lymphoma

Abstract

Background: Interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene-1 (MUM1) is a member of the interferon regulatory factor family of transcriptional factors. Although IRF4/MUM1 expression is associated with aggressiveness of B-cell lymphoma and multiple myeloma, the prognostic value of IRF4/MUM1 expression in peripheral T-cell lymphoma (PTCL) is unclear. Methods: We analyzed a tissue array from 69 patients diagnosed with PTCL. The expression levels of IRF4/MUM1 and associated proteins such as MYC and Ikaros were analyzed by immunohistochemistry. Samples were classified by IRF4/MUM1 expression into a negative group (less than 5% of all tumor cells staining positive) or a positive group (≥ 5% of all tumor cells staining positive). Results: IRF4/MUM1 expression was observed in 33% of all patients (23/69), most frequently in patients with anaplastic large cell lymphoma (ALCL, 78%, 7/9). Patients with PTCL, not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) showed expression rates of 33% (9/28) and 50% (4/8), respectively, whereas only 3 patients with extranodal NK/T-cell lymphoma (12%, 3/24) showed positive staining. The percentage of IRF4-positive tumor cells was significantly associated with the percentage of MYC-positive tumor cells (R: 0.410, P=0.013). Comparison of survival outcomes revealed that the IRF4/MUM1-positive group exhibited worse survival than the IRF4/MUM1-negative group; moreover, IRF4/MUM1-positive patients with a high level of MYC expression had the worst survival of all patients with nodal PTCL (PTCL-NOS, AITL, and ALCL; n=45) (P < 0.05). Conclusions: IRF4/MUM1 expression was associated with poor survival outcomes in PTCL, implying that this gene is a potential therapeutic target.