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系统生物学用于在急性髓性白血病中发现药物标

Svetlana Novikova¹, Tatiana Tolstova¹, Leonid Kurbatov¹

¹Institute of Biomedical Chemistry, Pogodinskaya 10, 119121 Moscow, Russia.

International journal of molecular sciences

|May 11, 2024

概括

将全转网红酸 (ATRA) 与新疗法结合使用可能改善急性髓性白血病 (AML) 治疗. 通过转录基因建模识别的CDK6等关键调节者的向为AML提供了一种新的治疗策略.

科学领域:

血液学血液学血液学
分子生物学分子生物学
基因组学就是基因组学.

背景情况:

急性髓性白血病 (AML) 的治疗可以通过将新型疗法与全转网红酸 (ATRA) 结合起来来增强.
了解ATRA诱导的分化分子机制对于开发更有效的AML疗法至关重要.

研究的目的:

确定提高AML治疗ATRA疗效的关键分子标.
为了分析不同AML细胞系对ATRA暴露随时间推移的转录基因反应.

主要方法:

用ATRA治疗的HL-60,NB4和K562细胞的基因组规模转录组分析.
转录基因数据的层次建模,以确定关键的调节基因.
使用基于TMT的质谱测量来验证基因表达变化的蛋白质层次分析.

主要成果:

在细胞系和时间点的ATRA反应中识别了差异表达基因 (DEGs).
确定了循环素依赖性激酶6 (CDK6),瘤缩因子α (TNF-α) 和CUX1作为关键调节剂.
在长期ATRA治疗后,观察到CDK6在转录基因和蛋白质基因水平的下调.

结论:

CDK6是ATRA治疗的AML细胞中的关键调节剂.
将ATRA (tretinoin) 与CDK6抑制剂 (palbociclib) 结合起来,为AML提供了一个潜在的替代治疗策略.

关键词:

在 HL-60 的情况下,它是 HL-60 的.K562 这里是K562 NB4 NB4 NB4 NB4 NB4 NB4 NB4 NB4 NB4 NB4 NB4 NB4 NB4 NB4 急性骨髓性白血病 (AML) 是一种急性骨髓性白血病.全转网红酸全转网红酸.颗粒细胞分化的分化.蛋白质组是一种蛋白质组.转录组 (transcriptome) 是一个转录组.

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