血清辅性是一种可向的脆弱性,由AML中的PSAT1抑制驱动
Ilias Sinanidis1, Panagiotis Tsakiroglou1, Benjamin Dubner1
1Division of Hematologic Malignancies and Bone Marrow Transplantation, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
bioRxiv : the preprint server for biology
|June 4, 2025
概括
一些急性髓性白血病 (AML) 是对血清素的辅性,这意味着它们不能产生它. 这些癌症抑制PSAT1,响应氨酸和甘氨酸的限制,可以通过饮食干预来准.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 生物化学 生物化学
背景情况:
- 血清代谢和血清合成途径 (SSP) 对癌细胞生长至关重要.
- 饮食限制血清素和甘氨酸 (SG) 显示出抑制某些癌症的潜力,但敏感性因素仍然不清楚,特别是在急性髓性白血病 (AML) 中.
研究的目的:
- 为了研究血清酶代谢在AML中的作用.
- 确定对AML饮食中的血清和甘氨酸限制敏感性的决定因素.
- 定义AML的一个独特的代谢亚型.
主要方法:
- 对人类AML细胞系和初级样本的分析.
- 评估血清素辅性及其与SSP酶表达 (PSAT1,PHGDH) 的相关性.
- 在体内和与venetoclax结合使用中对SG限制的反应的评估.
- MECOM重新排列与PSAT1抑制的相关性.
主要成果:
- 一个AML的子集表现出血清辅性,其特点是抑制PSAT1和无法合成血清.
- 这些血清辅性AML在体内对SG限制做出了反应,并通过PSAT1恢复得到拯救.
- 具有SF3B1 K700E突变的AML显示出对PHGDH的额外依赖.
- 在血清辅性AML中,SG限制与venetoclax协同作用.
- 麦科姆重组与PSAT1抑制和血清素辅助性强烈相关.
结论:
- 已经确定了一种独特的依赖外部血清的AML代谢亚型.
- 这种亚型的特点是PSAT1抑制和对SG限制的敏感性.
- 向血清代谢,特别是通过SG限制,代表了这种AML亚型的有前途的治疗策略.
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