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铁化剂deferasirox通过通过线粒体ROS调节NF-kB活性来影响骨髓分化

Nathan E Jeffries¹, Daniel Sadreyev¹, Elizabeth C Trull¹

¹Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

British journal of haematology

|September 27, 2024

概括

铁化剂deferasirox (DFX) 根据细胞类型对髓状细胞成熟有不同的影响. 通过影响线粒体的活性氧物种和基因表达,DFX会损害中性粒细胞的成熟.

科学领域:

血液学血液学血液学
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

德菲拉西洛克斯 (DFX) 治疗铁过载,并有利于骨髓质疏松综合征 (MDS) 患者.
核因子-kappa B (NF-kB) 信号传递是DFX在MDS中的影响的一个拟议机制.
之前的研究集中在DFX对造血原始体的影响上.

研究的目的:

研究DFX对髓状细胞成熟的表型和转录效应.
在小鼠和人类模型中分析DFX在髓分化的不同阶段的影响.

主要方法:

使用了小鼠和人类髓状细胞模型.
采用了单细胞转录组分析.
评估了线粒体反应性氧物种 (ROS) 生产和NF-kB通路调节.

主要成果:

根据分化阶段,DFX的作用有所不同,对原生细胞和中性粒细胞的影响不同.
DFX在中性粒细胞中增加了线粒体ROS的产生,这种效应因缺氧而减少.
DFX降低了原始细胞中的NF-kB和MYC标,以及中性粒细胞中的PU.1标.

结论:

DFX对髓状细胞分化的阶段依赖性影响.
似乎DFX会影响带中性粒细胞的终端成熟.
了解这些机制可以完善MDS的DFX治疗策略.

关键词:

在 MDS MDS 中.在 NF-KB 中.农细胞细胞形成的原因化化化化铁是铁,铁是铁,铁是铁.骨髓形成 (myelopoiesis) 是一种形成骨髓的过程.

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