早期T细胞前体急性淋巴细胞白血病的蛋白质组学景观揭示了缺陷的氧化酸化特征
Miaomiao Liu1, Tianyi Chen1, Xiangjie Lin2
1State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Cell reports. Medicine
|February 4, 2026
概括
早期T细胞前体急性淋巴细胞白血病 (ETP-ALL) 具有独特的代谢特征. 用二乙酸盐向氧化酸化 (OxPhos) 显示出这种高风险白血病的治疗前景.
科学领域:
- 血液学 血液学 血液学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 早期T细胞前体急性淋巴细胞白血病 (ETP-ALL) 是一个高风险的亚型,蛋白质组数据有限.
- 了解ETP-ALL的分子机制对于开发向疗法至关重要.
研究的目的:
- 为了描述ETP-ALL的蛋白质和代谢情景.
- 研究ETP-ALL中向氧化酸化 (OxPhos) 的治疗潜力.
- 为了确定ETP-ALL的新生物标志物.
主要方法:
- 集成的4D无标签蛋白质组分析.
- 单细胞RNA测序 (scRNA-seq) 是一种方法.
- 用二乙酸盐进行药理干预在体外和体内异种移植模型.
主要成果:
- ETP-ALL表现出明显的分子特征,具有严重的OxPhos缺乏,包括减少线粒体ATP合成和电子运输链 (ETC) I和IV复合体.
- 与分化T细胞相比,类似干细胞ETP-ALL种群的ETC活性明显较低.
- 二乙酸盐治疗恢复了OxPhos,抑制了白血病的扩散,并通过ROS介导的内质网膜应激减少了异种移植.
- CD109被确定为区分ETP-ALL的免疫类型标记物,并识别了易受二乙酸盐影响的子组.
结论:
- 线粒体调节失调,特别是OxPhos缺乏,是ETP-ALL发病的一个关键特征.
- 用二乙酸盐向OxPhos是ETP-ALL的可行的治疗策略.
- CD109是一种有前途的生物标志物,用于识别ETP-ALL患者,这些患者可能会从OxPhos向治疗中受益.
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