骨髓内皮原生细胞的重塑促进了在急性髓性白血病完全缓解期间的正常血液形成
Tong Xing1,2, Li-Juan Hu1, Hong-Yan Zhao1
1Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, China.
Nature communications
|December 31, 2024
概括
急性髓性白血病 (AML) 损害了骨髓的微环境,特别是内皮原生细胞 (EPC). 缓解后,EPC功能部分恢复,支持正常的血液形成,并且可以通过N-乙-L-氨酸 (NAC) 进一步改善.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 干细胞生物学 干细胞生物学
背景情况:
- 急性髓性白血病 (AML) 破坏了支持血造干细胞 (HSC) 的骨髓 (BM) 微环境.
- 在AML缓解后,BM微环境的支持正常血液形成的能力在很大程度上仍未被探索.
研究的目的:
- 在AML患者中实现完全缓解 (CR) 后,研究白血病修饰的BM微环境的重塑,重点是内皮前体细胞 (EPC),在AML患者中实现完全缓解后.
- 评估N-乙-L-氨酸 (NAC) 在CR后改善BM微环境功能的潜力.
主要方法:
- 从AML患者和CR患者的BM EPC分析.
- 评估EPC功能,包括血管新生和活性氧物种 (ROS) 水平.
- 对BM EPCs的转录组分析.
- 在AML小鼠模型化疗后评估BM血管和血液形成.
主要成果:
- 亚ML患者表现出减少和功能障碍的BM EPCs,血管生成受损和ROS升高.
- 在CR后,BM EPCs显示部分功能恢复,改善了HSC支持能力和减少了白血病支持能力.
- NAC治疗部分重塑了功能障碍的EPC,并改善了它们的功能.
- 转录组分析显示,在CR之后,白血病修饰的BM EPCs恢复到接近正常的特征.
- 在CR后的小鼠模型中,BM血管和正常血液形成被逆转.
结论:
- 经白血病修饰的BM微环境,特别是EPCs,可以经历部分重塑,以支持AML缓解后的正常血液形成.
- 在AML中,EPC功能障碍与血管生成受损和高ROS有关,这可以被NAC部分改善.
- 这些发现提供了关于AML后BM微环境恢复的见解,并突出了NAC作为增强这一过程的潜在治疗剂.
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