Interferon Regulatory Factor 4 Orchestrates The Response To B-Cell Receptor In Chronic Lymphocytic Leukemia Cells By Regulating Ikaros

Chronic lymphocytic leukemia (CLL) accounts for about 30% of all adult leukemias and is the most common hematologic malignancy in the Western countries. Interferon regulatory factor 4 (IRF4, also known as MUM1) is a transcriptional regulator of immune system development and function. Different IRF4 concentrations underlie the generation of alternative cell fate in mature B cells localized in secondary lymphoid organs, i.e. IRF4 “kinetic control” model. IRF4 at lower levels promotes germinal center formation and class switch recombination, whereas at higher levels IRF4 inhibits Bcl-6 and induces Blimp-1 to facilitate plasma cell development. Recent studies suggest a possible role of IRF4 in CLL pathogenesis. In New Zealand Black (NZB) IRF4+/- mouse model, CLL development is dramatically accelerated and IRF4+/- CLL cells showed hyper-responsiveness to B-cell receptor (BCR) activation.