Agnarelli Alessandro, Chevassut Tim, Mancini Erika J
School of Life Sciences, Biochemistry Department, University of Sussex, Falmer, Brighton, BN1 9QG, United Kingdom.
Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom.
Leuk Res. 2018 Sep;72:52-58. doi: 10.1016/j.leukres.2018.07.025. Epub 2018 Aug 3.
Multiple Myeloma (MM) is an incurable hematologic malignancy characterized by abnormal proliferation of plasma cells. Interferon Regulatory Factor 4 (IRF4), a member of the interferon regulatory family of transcription factors, is central to the genesis of MM. IRF4 is highly expressed in B cells and plasma cells where it plays essential roles in controlling B cell to plasma cell differentiation and immunoglobulin class switching. Overexpression of IRF4 is found in MM patients' derived cells, often as a result of activating mutations or translocations, where it is required for their survival. In this review, we first describe the roles of IRF4 in B cells and plasma cells and then analyse the subversion of the IRF4 transcriptional network in MM. Moreover, we discuss current therapies for MM as well as direct targeting of IRF4 as a potential new therapeutic strategy.
多发性骨髓瘤（MM）是一种无法治愈的血液系统恶性肿瘤，其特征为浆细胞异常增殖。干扰素调节因子4（IRF4）是转录因子干扰素调节家族的成员，在MM的发生过程中起核心作用。IRF4在B细胞和浆细胞中高表达，在控制B细胞向浆细胞分化以及免疫球蛋白类别转换中发挥重要作用。在MM患者来源的细胞中发现IRF4过表达，这通常是激活突变或易位的结果，IRF4是这些细胞存活所必需的。在本综述中，我们首先描述IRF4在B细胞和浆细胞中的作用，然后分析MM中IRF4转录网络的颠覆情况。此外，我们讨论了MM的当前治疗方法以及将IRF4作为潜在新治疗策略的直接靶向治疗。
