骨髓因急性髓性白血病的不同炎症条件及其对进展的影响
Valentina R Minciacchi1,2, Christina Karantanou1, Jimena Bravo1
1Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.
Blood advances
|July 12, 2024
概括
在急性髓性白血病 (AML) 中,瘤缩因子-α (TNF-α) 降低附录素A5 (ANXA5),促进炎症和白血病生长. 抑制前列腺素E2 (PGE2) 可能有利于AML患者的炎症性疾病.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 炎症在固体瘤中的作用已知,但对白血病的影响不太清楚.
- 结蛋白素A5 (ANXA5) 在急性髓性白血病 (AML) 的骨髓微环境 (BMM) 和慢性髓性白血病中表达不同.
- 这项研究调查了影响BMM内的AML进展的炎症机制.
研究的目的:
- 阐明AML炎症的调节电路,重点关注ANXA5和前列腺素E2 (PGE2) 的作用.
- 探索针对AML炎症途径的治疗潜力.
主要方法:
- 利用AML的小鼠模型并检查BMM中的ANXA5表达.
- 研究了AML衍生的瘤亡因子-α (TNF-α) 对ANXA5水平和随后的炎症媒介产生的影响 (PGE2).
- 在AML细胞中分析了信号通路 (β-catenin,HIF-1α),并在移植模型中评估了治疗干预措施.
主要成果:
- 在BMM中,AML衍生的TNF-α剂量依赖性降低了ANXA5,导致PGE2水平升高和炎症微环境.
- 通过其EP4受体,PGE2增强了AML细胞中的β-catenin和HIF-1α信号传递,促进了对PGE2敏感的AML生长.
- 人类AML活检显示较低的ANXA5和较高的PGE2表达与其他血液恶性瘤相比.
- 与单独的cytarabine相比,用celecoxib (一种COX2抑制剂) 加上cytarabine治疗改善了敏感的AML模型中的存活率.
结论:
- 一个TNF-α/ANXA5/NF-κB/COX2/PGE2炎症回路显著影响AML进展在一个差异和循环的方式.
- 患有"炎症性AML"的患者可能会从抗炎药物中受益,作为标准治疗的辅助疗法.
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