循环节律和骨髓脂肪组织中的aryl碳化合物受体交叉,以及白血病的含义
Bihter Muratoğlu1,2, Cansu Özdemir3,4, Cemil Can Eylem5
1Center for Stem Cell Research and Development (PEDI-STEM), Hacettepe University, 06100, Sihhiye, Ankara, Turkey.
Scientific reports
|May 11, 2025
概括
白血病细胞改变骨髓脂肪细胞以生存. 这项研究揭示了烯碳化合物受体 (AhR) 信号如何影响白血病中的昼夜节律和脂质代谢,提供了新的治疗点.
科学领域:
- 血液学 血液学 血液学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 白血病细胞利用骨髓微环境生存,骨髓脂肪组织 (BMAT) 的脂解起着关键作用.
- 芬科尼贫血 (FA) 作为研究白血病转变的模型,因为它对急性髓性白血病 (AML) 的倾向.
研究的目的:
- 研究由白血病细胞调节骨髓微环境的基础分子机制,重点研究BMAT衍生中酶体干/干细胞 (MSCs).
- 探索基碳化合物受体 (AhR) 信号传递的作用及其与白血病发病过程中的昼夜节律和脂质代谢的相互作用.
主要方法:
- 来自健康捐赠者 (HD),AML和FA患者的BMAT-MSC的综合多奥米克分析.
- 使用StemRegenin1 (SR1) 抑制AhR信号,观察其对基因表达和细胞通路的影响.
- 对基因表达,代谢物和脂质的分析,包括昼夜节律和脂质代谢相关的基因.
主要成果:
- 来自FA和AML患者的BMAT-MSC显示了上皮细胞-介质细胞转变 (EMT) 基因表达的增加,表明向癌症相关纤维细胞的转变.
- 治疗SR1调节昼夜节律和脂质代谢基因,在AML BMAT-MSC中观察到调节障碍.
- FABP5和CD36被上调,这表明了一种涉及FABP5在AhR介导的昼夜调节和CD36作为潜在的FABP5合作伙伴的新机制.
结论:
- 这项研究揭示了白血病中BMAT-MSC利基内的AhR信号传递,昼夜节律和脂质代谢之间的复杂相互作用.
- 这些发现为白血病病原性提供了新的见解,并确定了AML和相关疾病的潜在治疗点.
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