向S100A9蛋白质会影响mTOR-ER的压力信号,并增加急性髓性白血病中venetoclax的敏感性
Rong Fan1,2, Hatice Satilmis1,2, Niels Vandewalle1,2
1Laboratory for Hematology and Immunology, Department of Biomedical Sciences, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, Building D, 1090, Brussel, Belgium.
Blood cancer journal
|December 18, 2023
概括
准与骨髓相关的蛋白质S100A9显示在急性骨髓白血病 (AML) 中具有治疗潜力. 抑制S100A9会增加亡并增强venetoclax的敏感性,提供新的AML治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 血液学 血液学 血液学
背景情况:
- 由于急性髓性白血病 (AML) 的异质性和有限的向治疗方法,它构成了重大挑战.
- 骨髓相关蛋白S100A9在AML中高度表达,表明其作为治疗点的潜力.
研究的目的:
- 研究针对S100A9在AML中的治疗效果和机制.
- 为了评估S100A9抑制与venetoclax结合用于AML治疗.
主要方法:
- 在AML细胞系和患者样本中利用了S100A9沉默 (siRNA) 和抑制剂tasquinimod.
- 评估了细胞亡,细胞活力,增殖,mTOR信号传递,内质网膜应激和代谢功能.
- 研究了S100A9针对性与venetoclax的协同效应.
主要成果:
- 沉默S100A9降低了AML细胞的活力和增殖,通过降低mTOR和ER压力信号诱导细胞亡.
- 塔斯基尼莫德模仿了这些对增殖和mTOR信号传递的影响,对细胞代谢有明显的影响.
- 结合S100A9向和venetoclax显著提高了敏感性,降低了BCL-2和c-MYC的调节.
结论:
- 在AML治疗中,S100A9是一个有前途的分子标.
- 塔斯奎尼莫德在AML中显示出治疗潜力,并值得在基于venetoclax的组合疗法中进行评估.
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