在无菌炎症反应期间,细胞亡抵抗性急性髓性白血病细胞中的线粒体功能障碍
Elena I Meshcheriakova1,2, Kirill S Krasnov1,3, Irina V Odinokova1
1Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia.
Biomolecules
|December 30, 2025
概括
炎症会在急性髓性白血病 (AML) 细胞中引发代谢变化,导致线粒体功能障碍并促进对亡的抵抗力. 这种AML细胞适应有助于在炎症性压力期间的生存.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 线粒体在能量代谢,亡和急性髓性白血病 (AML) 中的炎症中起着至关重要的作用.
- 细胞亡抵抗是AML的标志,导致治疗失败.
研究的目的:
- 在无菌性预炎症激活下,研究抗亡AML细胞中的线粒体变化.
- 了解炎症性压力期间AML细胞的代谢重编程.
主要方法:
- 谱流量计,qPCR,西式斑点,基因表达分析,流细胞计,传输电子显微镜和细胞呼吸分析.
- 在3D高密度培养中对AML细胞进行体外无菌性前炎性激活.
主要成果:
- 耐灭性AML细胞显示氧化酸化和三酸循环基因活性降低.
- 观察到线粒体呼吸减弱,PINK1/Parkin水平降低,反应性氧物种增加.
- 发现了致病性线粒体形态变化,包括DRP1升高和中小线粒体增加,以及乳酸积累.
结论:
- 无菌性促炎激活诱导AML细胞中的代谢重塑和线粒体功能障碍.
- 这种重编程可能会增强白血病细胞的持久性,并有助于细胞灭亡抵抗.
- 这项研究建立了一个研究AML细胞代谢和抗亡机制的模型.
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