感受受体在白血病中的独特和可向作用
Raquel S Pereira1, Rahul Kumar1, Alessia Cais2
1Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.
Nature communications
|October 6, 2023
概括
感应受体 (CaSR) 影响白血病干细胞在骨髓微环境中的位置和自我更新. 向CaSR可能通过改变细胞外反应来增强白血病治疗.
科学领域:
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
- 生物化学 生物化学
背景情况:
- 造血干细胞 (HSC) 存在于骨髓微环境中 (BMM).
- HSCs通过G蛋白结合感应受体 (CaSR) 响应细胞外 ([eCa2+]) .
研究的目的:
- 在BMM中调查CaSR在白血病进展中的作用.
- 确定MLL-AF9+急性髓性白血病 (AML) 和BCR-ABL1+白血病之间的CaSR信号是否不同.
- 评估CaSR作为AML的潜在治疗点.
主要方法:
- 在BMM中分析梯度.
- 评估CaSR对MLL-AF9 AML细胞局部和白血病干细胞 (LSC) 数量的影响.
- 研究CaSR与胺A的相互作用以及信号通路 (pERK,β-catenin,c-MYC) 的调制.
- 在临床前模型中对联合治疗 (cytarabine + CaSR 抑制) 的评估.
主要成果:
- 在BMM中存在梯度,在白血病中具有差异性的[eCa2+]和CaSR反应.
- 由于CaSR缺乏,AML LSC减少了6.5倍.
- CaSR与胺A相互作用,影响茎状因素并调节关键信号通路.
- 组合治疗显示出潜在的优势,超过单独的cytarabine.
结论:
- CaSR是白血病进展中的差异性和可向性因素.
- CaSR通过BMM [eCa2+]信号影响AML LSC的自我更新.
- 向CaSR为AML提供了一个潜在的治疗策略.
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