Department of Medicine, Division of Hematology/Oncology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA.
O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA.
Adv Exp Med Biol. 2024;1459:379-403. doi: 10.1007/978-3-031-62731-6_17.
Myocyte enhancer factor 2 (MEF2) is a key transcription factor (TF) in skeletal, cardiac, and neural tissue development and includes four isoforms: MEF2A, MEF2B, MEF2C, and MEF2D. These isoforms significantly affect embryonic development, nervous system regulation, muscle cell differentiation, B- and T-cell development, thymocyte selection, and effects on tumorigenesis and leukemia. This chapter describes the multifaceted roles of MEF2 family proteins, covering embryonic development, nervous system regulation, and muscle cell differentiation. It further elucidates the contribution of MEF2 to various blood and immune cell functions. Specifically, in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), MEF2D is aberrantly expressed and forms a fusion protein with BCL9, CSF1R, DAZAP1, HNRNPUL1, and SS18. These fusion proteins are closely related to the pathogenesis of leukemia. In addition, it specifically introduces the regulatory effect of MEF2D fusion protein on the proliferation and growth of B-cell acute lymphoblastic leukemia (B-ALL) cells. Finally, we detail the positive feedback loop between MEF2D and IRF8 that significantly promotes the progression of acute myeloid leukemia (AML) and the importance of the ZMYND8-BRD4 interaction in regulating the IRF8 and MYC transcriptional programs. The MEF2D-CEBPE axis is highlighted as a key transcriptional mechanism controlling the block of leukemic cell self-renewal and differentiation in AML. This chapter starts with the structure and function of MEF2 family proteins, specifically summarizing and analyzing the role of MEF2D in B-ALL and AML, mediating the complex molecular mechanisms of transcriptional regulation and exploring their implications for human health and disease.
肌细胞增强因子 2（MEF2）是骨骼、心脏和神经系统发育中的关键转录因子（TF），包括四个同工型：MEF2A、MEF2B、MEF2C 和 MEF2D。这些同工型对胚胎发育、神经系统调节、肌肉细胞分化、B 和 T 细胞发育、胸腺细胞选择以及对肿瘤发生和白血病的影响有重要作用。本章描述了 MEF2 家族蛋白的多方面作用，涵盖了胚胎发育、神经系统调节和肌肉细胞分化。它进一步阐明了 MEF2 对各种血液和免疫细胞功能的贡献。具体来说，在 B 细胞前体急性淋巴细胞白血病（BCP-ALL）中，MEF2D 异常表达并与 BCL9、CSF1R、DAZAP1、HNRNPUL1 和 SS18 形成融合蛋白。这些融合蛋白与白血病的发病机制密切相关。此外，它还特别介绍了 MEF2D 融合蛋白对 B 细胞急性淋巴细胞白血病（B-ALL）细胞增殖和生长的调节作用。最后，我们详细介绍了 MEF2D 和 IRF8 之间的正反馈环，该环显著促进了急性髓细胞白血病（AML）的进展，以及 ZMYND8-BRD4 相互作用在调节 IRF8 和 MYC 转录程序中的重要性。MEF2D-CEBPE 轴被强调为控制 AML 中白血病细胞自我更新和分化阻滞的关键转录机制。本章从 MEF2 家族蛋白的结构和功能开始，特别总结和分析了 MEF2D 在 B-ALL 和 AML 中的作用，介导转录调控的复杂分子机制，并探讨了其对人类健康和疾病的意义。
