The role of IrF-4 and IRF-8 in the Pathogenesis of B-cell neoplasm

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IRF-4 and IRF-8 are the transcription factors of IRF family playing the important role in the development of B-lymphocytes. The expression of IRF-4 has been recognized as one of the prognostic factor for diffuse large B-cell lymphoma (DL). On the other hands, the lack of IRF-8 induces myeloid leukemia. The aim of this study is to approach the question if these molecules act in the pathogenesis of B-cell malignancies. First of all, the expression of IRF-4 and IRF-8 was tested by semi-quantitative RT-PCR. Forty-two DL and 32 follicular lymphoma (FL) tumors were analyzed. Both IRF-4 and IRF-8 gene were detected in most samples. Higher IRF-8 expression than IRF-4 was seen in 13 DL samples (30.9%) and 16 in FL samples (69.5%). Interestingly, the overall survival was better in IRF-4<IRF-8 patients (statistically not significant). These results suggests that DL could be categorized based on the expression of these factors. Next, to identify protein of these factors directory in single tumor cell, immunohistochemistry was challenged. However, it was unable to gain the clear results because of the lack of good antibody for human IRF-8. Recently, IRF-4 and 8 are reported to cooperate with bc1-2 during the pathogenesis of hematological malignancies. Bcl-2 is an apoptotic factor forming chimera gene with IgH resulted by the translocation (14; 8) typically found in FL. Also, this protein is over expressed in high risk DL cells. To clarify the role of this translocation in DL, FISH for bcl2/IgH, as well as immunohistochemistry for bc1-2 protein were performed on 35 samples from high risk DL patients. Bc12/IgH fusion was detected in 57.1% of samples from dead cases. On the other hands, neither bc12/IgH fusion and bc1-2 expression was detected in 71.4% of tumor cells from survivors, suggesting that translocation (14; 18) plays key role in refractory DL.