SOCS3作为抑癌基因，通过负反馈调节JAK/STAT信号通路来抑制肿瘤细胞的生长。本研究旨在探讨DNMT介导的SOCS3甲基化在AML发生发展中的生物学功能和机制。收集70名AML患者和20名健康志愿者的骨髓样本。采用RT-qPCR、Western blot、MS-PCR检测各基因的表达及甲基化状态，CCK-8、流式细胞仪检测白血病细胞系生长及凋亡率。通过基因转染和基因敲除观察AML细胞系SOCS3基因表达和甲基化状态变化的影响。AML初始治疗组SOCS3甲基化率显着高于缓解组和正常对照组（60 % 与 0%、0%）。 SOCS3甲基化组中SOCS3的表达量显着低于非甲基化组和对照组,而DNMT1、DNMT3a、p-JAK2、p-STAT3、p-STAT5的表达量显着高于非甲基化组和对照组。非甲基化组和对照组。去甲基化处理、SOCS3转染和DNMT3a敲低可上调SOCS3的表达，从而减少白血病细胞系的增殖并增加其凋亡。DNMTs介导的SOCS3甲基化促进AML的发生和发展，可作为潜在的生物标志物用于 AML 的诊断和疗效评估。© 2023 John Wiley

As a tumor suppressor gene, SOCS3 inhibits the growth of tumor cells by regulating JAK/STAT signaling pathway through negative feedback. This study aimed to investigate the biological function and mechanism of SOCS3 methylation mediated by DNMTs in the development of AML.Bone marrow samples were collected from 70 AML patients and 20 healthy volunteers. The expression and methylation status of each gene were detected by RT-qPCR, western blot and MS-PCR, and the growth and apoptosis rate of leukemia cell lines were detected by CCK-8 and flow cytometry. The effects of changes in SOCS3 gene expression and methylation status of AML cell lines were observed by gene transfection and gene knockdown.The methylation rate of SOCS3 in AML initial treatment group was significantly higher than that in the remission group and the normal control group (60% vs. 0%, 0%). The expression of SOCS3 in the SOCS3 methylation group was significantly lower than that in the non-methylated group and control group, while the expression of DNMT1, DNMT3a, p-JAK2, p-STAT3 and p-STAT5 were significantly higher than those in the non-methylated group and control group. Demethylation treatment, SOCS3 transfection and DNMT3a knockdown could up-regulate the expression of SOCS3, which decreased the proliferation and increased the apoptosis of leukemia cell lines.SOCS3 methylation mediated by DNMTs promotes the occurrence and development of AML and can be used as a potential biomarker for the diagnosis and efficacy evaluation of AML.© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.