急性髓性白血病（AML）是最具侵袭性的造血系统恶性肿瘤，其特征是骨髓内髓系前体细胞的不受控制增殖。抑癌基因CYLD是一种去泛素化酶，能够抑制巨噬细胞中的炎症反应。巨噬细胞通过其专业吞噬功能，在对外来物质和循环癌细胞的防御中发挥着核心作用。目前对CYLD对人类巨噬细胞生物特性的影响及其在AML中的作用了解甚少。因此，本研究旨在探讨CYLD是否影响健康个体和AML患者的巨噬细胞功能。为此，招募了92名新诊断的AML患者和80名健康对照者。通过实时荧光定量PCR评估了与炎症相关基因的mRNA表达水平，通过流式细胞术评估了细胞成熟、吞噬作用和凋亡，通过酶联免疫吸附检测评估了炎症性细胞因子的分泌。结果显示，低CYLD表达的AML患者在FAB分型中M4/M5亚型的比例显著高于其他亚型。低CYLD表达与年龄较大的患者和AML中乳酸脱氢酶（LDH）水平升高紧密相关。此外，正常巨噬细胞接受CYLD小干扰RNA处理后，STAT-1的激活程度显著增加，细胞成熟标志物的表达和白细胞介素-6（IL-6）的产生也增加，同时细胞凋亡和吞噬能力受到抑制。而在AML M4/M5b中，巨噬细胞的吞噬能力较健康对照组在CYLD小干扰RNA转染后通过STAT1信号通路显著增强。综上所述，CYLD对巨噬细胞功能的抑制作用有望影响AML的免疫应答。版权：© 2023 Huyen等人。本文为开放获取文章，根据创作共用许可证分发，只要原作者和资源出处被指明，可以在任何媒体上自由使用、分发和复制该文章。

Acute myeloid leukemia (AML) is the most aggressive hematopoietic malignancy characterized by uncontrolled proliferation of myeloid progenitor cells within the bone marrow. Tumor suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme, which suppresses inflammatory response in macrophages. Macrophages have a central role in the defense against foreign substances and circulating cancer cells by their professional phagocytic capacity. Little is known about contributions of CYLD to changes in biological properties of human macrophages and its involvement in AML. The present study, therefore, explored whether macrophage functions in healthy individuals and AML patients are influenced by CYLD. To this end, ninety-two newly diagnosed AML patients and 80 healthy controls were recruited. The mRNA expression levels of inflammation-related genes were evaluated by real-time PCR, cell maturation, phagocytosis and apoptosis assays by flow cytometry and secretion of inflammatory cytokines by ELISA. As a result, AML patients with the low CYLD expression were significantly higher in M4/M5 than other subtypes according to the FAB type. The low CYLD expression was also closely associated with older patients and enhanced level of LDH in AML. Moreover, treatment of normal macrophages with CYLD siRNA enhanced activation of STAT-1, leading to increases in expressions of maturation markers and IL-6 production as well as suppression in cell apoptosis and phagocytosis, while macrophage phagocytosis from AML M4/M5b was higher than that from healthy controls upon CYLD siRNA transfection through STAT1 signalling. In conclusion, the inhibitory effects of CYLD on macrophage functions are expected to affect the immune response in AML.Copyright: © 2023 Huyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.