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Updated: Feb 19, 2026

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在FLT3-ITD急性髓性白血病细胞模型中调节代谢信号以减轻卡博桑提尼布耐药性

Yu-Hsuan Fu¹, Kit Man Ng¹, Chi-Yang Tseng¹

¹Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.

Cell death discovery

|February 17, 2026

概括

急性髓性白血病 (AML) 的耐药性是一个挑战. 使用PI3K/mTOR或HSP90抑制剂准代谢重编程可以克服FLT3-ITD+AML中的卡博桑提尼布耐药性.

科学领域:

血液学血液学血液学
癌症生物学癌症生物学
分子瘤学分子瘤学

背景情况:

药物耐药性是急性髓性白血病 (AML) 治疗的一个重要障碍.
针对AML的向疗法,包括FLT3抑制剂,由于获得的耐药性而面临挑战.
了解抵抗机制对于开发有效的治疗策略至关重要.

研究的目的:

建立和表征卡博赞提尼布耐药的FLT3-ITD+AML细胞系.
调查卡博桑提尼布耐药性背后的分子和代谢变化.
确定潜在的治疗策略,以克服AML中的卡博桑提尼布耐药性.

主要方法:

产生抗卡博桑提尼布的AML细胞系 (MV4-11-XR,Molm13-XR).
突变分析 (FLT3),细胞增殖,殖民地形成,以及信号通路评估 (p-FLT3,ERK,STAT5,AKT).
转录基因分析,代谢分析 (糖解,氧化酸化) 和化/体外药物查.

主要成果:

耐药细胞表现出对其他FLT3抑制剂的交叉耐药性,并获得了FLT3突变 (D835Y,删除).
在耐药细胞中观察到增加的增殖,殖民地形成和构成FLT3信号.
显著的代谢重编程,包括增强的糖解和受损的氧化酸化,被确定为耐药性的标志.

结论:

代谢失调是推动FLT3-ITD+AML中卡博桑提尼布耐药性的关键机制.
双重PI3K/mTOR抑制剂奥米帕利西布和HSP90抑制剂雷迪西科尔逆转了代谢重编程.
与卡博赞提尼布和奥米帕利西布或雷迪科尔的联合治疗显示出克服AML药物耐药性的治疗潜力.

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