白血病给健康的造血干细胞和原始细胞留下了持久的印记
Ding-Wen Chen1, Julie M Schrey1, Eric K Wafula2
1Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Cancer letters
|February 28, 2025
概括
在急性髓性白血病 (AML) 中的炎症可持续地重编程健康的造血干细胞和原始细胞 (HSPC). 这些重新编程的HSPCs表现出改变的基因表达和新陈代谢,影响它们对未来挑战的反应.
科学领域:
- 血液学 血液学 血液学
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
背景情况:
- 造血干细胞和原始细胞 (HSPCs) 可以对以前的暴露产生记忆.
- 炎症是血液恶性瘤的关键特征,如急性髓性白血病 (AML).
- 骨髓 (BM) 利基在调节HSPC功能方面发挥着至关重要的作用.
研究的目的:
- 为了调查AML中的炎症性骨髓 (BM) 微环境是否能持续地重编程健康的居民HSPC.
- 了解癌症相关炎症对正常干细胞的长期影响.
主要方法:
- 使用了一种涉及AML的转化相关小鼠模型,其中涉及HSPC中可诱导的MLL-AF9转位.
- 生成的造血机象,包括健康的HSPC和AML携带的HSPC,以模拟恶性瘤和缓解.
- 在AML暴露后的HSPC中分析了转录组变化,代谢转移 (糖解) 和染色质可访问性.
主要成果:
- 暴露于AML爆发引发了持久的转录基因变化,并在缓解期间在健康的HSPC中转向糖溶性代谢.
- 经验丰富的动物的二次AML挑战导致了改变的炎症和代谢基因表达.
- 这些HSPC的功能变化与改变的染色质可访问性相关.
结论:
- 这项研究提供了第一个证据,即健康的HSPCs可以在癌症微环境中经历持久的炎症重编程.
- 这些发现表明,与癌症相关的炎症可以在干细胞池中留下持久的印记,可能会影响未来的健康结果.
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