蛋白精氨酸甲基转移酶在多发性骨髓瘤中的新作用。

Molecular therapy. Oncology Pub Date : 2025-05-26 eCollection Date: 2025-06-18 DOI:10.1016/j.omton.2025.201003
Sajida Fady Qaddoura, Enze Liu, Brian A Walker, Ngoc Tung Tran
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引用次数: 0

摘要

多发性骨髓瘤(MM)是一种以骨髓中异常浆细胞克隆扩增为特征的浆细胞癌。这些恶性细胞过度拥挤骨髓,扰乱正常的造血功能,产生过量的免疫球蛋白,导致严重的临床表现。尽管治疗取得了重大进展,但复发/难治性MM仍然无法治愈。蛋白精氨酸甲基化是由蛋白精氨酸甲基转移酶(PRMTs)催化的一种关键的翻译后修饰,参与调节各种细胞过程。PRMT的异常表达与包括MM在内的许多癌症的不良预后密切相关。在PRMT家族中,PRMT1、PRMT4 (CARM1)和PRMT5已成为MM的潜在治疗靶点。本文将首先探讨PRMT在MM中的表达模式,并评估其与疾病预后的关系。然后,我们将全面概述这些PRMT在MM病理中的功能,讨论目前在临床试验中评估的PRMT抑制剂的发展,并提供针对PRMT在MM临床治疗中的潜力的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Emerging roles of protein arginine methyltransferase in multiple myeloma.

Multiple myeloma (MM) is a cancer of plasma cells characterized by the clonal expansion of abnormal plasma cells in the bone marrow. These malignant cells overcrowd the bone marrow, disrupt normal hematopoiesis, and produce excessive amounts of immunoglobulins, leading to severe clinical manifestations. Despite significant advancements in treatment, relapsed/refractory MM remains incurable. Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is a critical post-translational modification involved in regulating various cellular processes. Aberrant expression of PRMTs has been strongly linked to poor prognosis in many cancers, including MM. Among the PRMT family, PRMT1, PRMT4 (CARM1), and PRMT5 have emerged as potential therapeutic targets for MM. This review will first explore the expression patterns of PRMTs in MM and assess their association with disease prognosis. We will then provide a comprehensive overview of the functions of these PRMTs in MM pathology, discuss the development of PRMT inhibitors currently being evaluated in clinical trials, and offer insights into the potential of targeting PRMTs for MM treatment in clinical settings.

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