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在急性髓性白血病中集成的m6A阅读器网络:预后建模,免疫调节和YTHDF3的功能验证

Fangmin Zhong¹, Zihao Wang¹, Jialin Huang¹

¹Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

International immunopharmacology

|December 5, 2025

概括

RNA N6-甲基氨酸 (m6A) 读者驱动急性髓性白血病 (AML) 的进展和免疫逃避. 针对读者YTHDF3并利用新的预后得分可以指导AML患者的风险适应治疗.

科学领域:

分子生物学分子生物学
癌症研究癌症研究
免疫学免疫学免疫学

背景情况:

RNA N6-甲基氨酸 (m6A) 修改在癌症中至关重要,但它们在急性髓性白血病 (AML) 中的作用尚未完全理解.
对于m6A阅读器对AML病原和患者结局的具体贡献需要进一步研究.

研究的目的:

阐明m6A读者在AML发展和预后中的集体作用.
开发一个预后工具,并在m6A读者网络中确定治疗目标.

主要方法:

从2680名AML患者的multiomics数据中获取m6A阅读器网络的地图.
使用机器学习开发了一个m6A阅读器活动评分 (m6ARS) 和一个28基因预后模型.
进行了功能性研究,以调查YTHDF3.0的致癌作用.

主要成果:

确定了与攻击性AML亚型和不良预后相关的m6A读者的协调上调.
升高的m6ARS与增加的增殖,减少的CD8+T细胞透和免疫逃避相关.
这种28基因模型准确地预测了多个队列中的患者结果,超过了传统因素.
鉴定出YTHDF3是一种致癌驱动物,通过稳定关键转录物来促进AML.

结论:

m6A阅读器网络是AML进展和免疫逃避的关键调节器.
开发的预后框架和m6ARS为风险分层和指导治疗提供了有价值的工具.
YTHDF3代表了AML的一个有前途的治疗点,将RNA表观遗传与临床应用联系起来.

关键词:

预测风险模型的预测风险模型.这就是YTHDF3的原因.m6A阅读器的使用

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