[线粒体转移对白血病进展的影响]
Wen-Jia Fang1,2, Biao Zhang1,2, Tao Cheng1,2
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
骨髓细胞将线粒体转移到白血病细胞,损害白血病细胞的功能和生存. 这种线粒体转移起到宿主防御机制的作用,防止急性髓性白血病 (AML) 的进展.
科学领域:
- 细胞生物学 细胞生物学
- 癌症新陈代谢 癌症新陈代谢
- 血液学 血液学 血液学
背景情况:
- 骨髓微环境在调节白血病细胞行为和进展方面发挥着至关重要的作用.
- 线粒体功能对于癌细胞的新陈代谢和生存至关重要,其在微环境中的调节还不太清楚.
- 急性髓性白血病 (AML) 是一种异质的血液性恶性瘤,白血病细胞和它们的位之间存在复杂的相互作用.
研究的目的:
- 研究骨髓微环境细胞在调节白血病细胞线粒体质量的作用.
- 揭示白血病进展背后的代谢机制,特别关注线粒体转移.
- 探索线粒体转移作为对抗AML的宿主防御机制的潜力.
主要方法:
- 使用MLL-AF9 (MA9) 融合蛋白过度表达,建立了急性髓性白血病 (AML) 的小鼠模型.
- 利用线粒体光记者小鼠 (mito-Dendra2) 来跟踪线粒体转移.
- 采用流细胞测量,光激活细胞分类 (FACS),功能测试,散装RNA测序,以及*在体外*的共培实验与介质细胞 (MSCs) 和内皮细胞 (ECs).
主要成果:
- 观察到骨髓细胞在AML小鼠模型中将线粒体转移到白血病细胞,随着AML的进展,转移减少.
- 接受转移线粒体的白血病细胞表现出反应性氧物种 (ROS) 和亡的增加,以及蛋白质翻译和殖民地形成能力的降低.
- 骨髓利基内的介质细胞 (MSC) 被确定为将线粒体转移到白血病细胞中的关键参与者,促进白血病细胞亡.
结论:
- 骨髓利基细胞可以将线粒体转移到白血病细胞,从而对MA9-诱导的AML模型中的白血病细胞存活和功能产生负面影响.
- 线粒体从骨髓细胞转移到白血病细胞似乎是一个抑制AML进展的宿主保护机制.
- 准线粒体转移通路可能是AML的新治疗策略.
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