转录异型多样性通过长读测序定义了急性髓性白血病的分子亚型和预后
Xiaoguang Shi1, Shuai Wang2, Shuting Yu2
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Cell reports
|September 4, 2025
概括
长读测序揭示了急性髓性白血病 (AML) 的新型转录异型,揭示了广泛的拼接异常. 这些发现确定了与患者预后相关的新型AML亚型,为精准医学铺平了道路.
科学领域:
- 基因组学
- 转录组学
- 癌症生物学
背景情况:
- 急性髓性白血病 (AML) 是一种具有显著临床异质性的复杂血液癌症.
- 了解AML的分子基础对于开发有效治疗至关重要.
研究的目的:
- 使用长读转录组测序全面分析AML的拼接异常.
- 识别新的转录异型及其作为AML分类和预后的生物标志物的潜力.
主要方法:
- 在60个AML骨髓样本上进行长读转录组测序 (牛津纳米孔技术).
- 使用液态染色体-双重质谱法识别和验证未注释的转录异型.
- 对RNA测序数据进行非负矩阵因子集群,以定义分子亚型.
主要成果:
- 检测广泛的AML特异性拼接异常.
- 识别了119,278个以前没有注释的转录异型,其中80,294个包含完整的开放阅读框架.
- 发现异型定义的AML亚型与患者的预后有很强的相关性.
结论:
- 替代拼接对AML的分子异质性有显著的贡献.
- 新的转录异型和拼接模式可以作为AML分类的潜在生物标志物.
- 这些发现支持推进精准医学,并开发基于拼接异常的AML向治疗方法.
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