氨酸依赖是慢性骨髓性白血病干细胞中治疗上可利用的脆弱性
Kevin M Rattigan1, Martha M Zarou1, Zuzana Brabcova1
1Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK.
EMBO reports
|July 25, 2023
概括
慢性髓性白血病 (CML) 细胞的生长依赖氨酸. 剥夺这些白血病干细胞 (LSC) 的氨酸或使用酶BCT-100有效地消除它们,提供了一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 白血病干细胞生物学
背景情况:
- 白血病细胞表现出代谢放松调节,导致营养物质依赖.
- 慢性髓性白血病 (CML) 细胞需要特定的营养物质来增殖.
研究的目的:
- 为了确定主要人类CML细胞的必需营养素.
- 为了调查CML中阿尔金林的依赖.
- 评估氨酸枯竭作为对CML白血病干细胞 (LSCs) 的治疗策略.
主要方法:
- 在临床前CML模型中氨基酸脱落屏幕.
- 在白血病 (MILE) 数据集中微阵列创新的分析.
- 稳定同位素追踪以评估尿素循环酶活性.
- 在体外和体内使用阿尔金因剥夺和BCT-10000的疗效研究.
主要成果:
- 鉴定出氨酸对人类原发性CML细胞至关重要.
- 在CML细胞中观察到降低的ASS1水平和抑制的尿素循环酶活性,表明了阿尔金因辅助性.
- 缺少氨酸阻断了CML CD34+细胞的增殖,并诱导了细胞亡.
- 在患者衍生异种移植模型中,BCT-100在减少LSC方面表现出高效.
结论:
- 氨酸枯竭是针对CML的一个有希望的策略.
- 准阿金代谢可以根除耐治疗白血病干细胞.
- BCT-100显示出对CML治疗的显著潜力.
更多相关视频
06:28Simplified Intrafemoral Injections Using Live Mice Allow for Continuous Bone Marrow Analysis
Published on: November 10, 2023
2.1K
09:01Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
14.0K
相关概念视频
Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Multipotency of Hematopoietic Stem Cells
3.1K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.1K
Regulation of Hematopoietic Stem Cells
3.2K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K
