Cancer Science Institute of Singapore, National University of Singapore, Singapore.
Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Exp Hematol. 2022 Oct;114:9-17. doi: 10.1016/j.exphem.2022.07.300. Epub 2022 Jul 29.
Dysregulation of transcription factor genes represents a unique molecular etiology of hematological malignancies. A number of transcription factors that play a role in hematopoietic cell development, lymphocyte activation, or their maintenance have been identified as oncogenes or tumor suppressors. Many of them exert oncogenic abilities in a context-dependent manner by governing the key transcriptional program unique to each cell type. IRF4, a member of the interferon regulatory factor (IRF) family, acts as an essential regulator of the immune system and is a prime example of a stage-specific oncogene. The expression and oncogenicity of IRF4 are restricted to mature lymphoid neoplasms, while IRF4 potentially serves as a tumor suppressor in other cellular contexts. This is in marked contrast to its immediate downstream target, MYC, which can cause cancers in a variety of tissues. In this review article, we provide an overview of the roles of IRF4 in the development of the normal immune system and lymphoid neoplasms and discuss the potential mechanisms of lineage- and stage-specific oncogenicity of IRF4.
转录因子基因的失调代表了血液系统恶性肿瘤独特的分子发病机制。许多在造血细胞发育、淋巴细胞激活或维持中发挥作用的转录因子已被确定为癌基因或肿瘤抑制因子。其中许多通过调节每种细胞类型特有的关键转录程序，以依赖于上下文的方式发挥致癌能力。IRF4 是干扰素调节因子 (IRF) 家族的成员，它是免疫系统的重要调节剂，是特定阶段癌基因的一个典型例子。IRF4 的表达和致癌性仅限于成熟的淋巴肿瘤，而在其他细胞环境中，IRF4 可能作为肿瘤抑制因子发挥作用。这与它的直接下游靶标 MYC 形成鲜明对比，后者可以在多种组织中引起癌症。在这篇综述文章中，我们概述了 IRF4 在正常免疫系统和淋巴肿瘤发育中的作用，并讨论了 IRF4 谱系和阶段特异性致癌性的潜在机制。
