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骨髓 stromal 细胞减少了低剂量细胞胺诱导的急性髓性白血病的分化

Tomislav Smoljo¹, Barbara Tomic¹, Hrvoje Lalic¹

¹Laboratory for Cell Biology, Department of Physiology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.

Frontiers in pharmacology

|November 13, 2023

概括

骨髓 stromal 细胞通过阻断癌细胞分化来阻碍急性髓性白血病 (AML) 中低剂量细胞氨基酸 (LDAC) 的有效性. 这就解释了为什么LDAC在患者中显示出有限的差异化.

科学领域:

血液学血液学血液学
在瘤学瘤学.
细胞生物学细胞生物学

背景情况:

低剂量细胞氨基酸 (LDAC) 是老年急性髓性白血病 (AML) 患者的标准治疗方法.
在AML中LDAC作用的机制尚未完全理解,特别是关于分化.
实验室研究表明,LDAC诱导了分化,但这种情况在体内很少见.

研究的目的:

为了研究骨髓 (BM) 层细胞对LDAC诱导的AML细胞分化的影响.
探索为什么在体外观察到的LDAC诱导的分化在体内没有复制.

主要方法:

联合培养的AML细胞系 (U937,MOLM-13) 和初级AML样本与MS-5 stromal细胞.
评估LDAC对细胞周期,DNA损伤和分化的影响.
转录组分析以确定分子变化.
药物抑制和中和抗体测试特定的途径 (CXCL12,TGF-β1,ROS).

主要成果:

MS-5 stromal细胞抑制了LDAC诱导的细胞周期停止,DNA损伤和AML细胞系的分化.
电流细胞减少了与细胞因子信号传递和氧化应激相关的基因的表达.
像CXCL12,TGF-β1或活性氧物种这样的特定途径不是这种抑制的主要媒介.
在初级AML-M4和MDS/AML样本中也观察到LDAC诱导的分化减少.

结论:

骨髓层瘤显著降低了由LDAC诱导的AML细胞的分化.
这种相互作用为在用LDAC治疗的AML患者中观察到的有限的终端分化提供了潜在的解释.
了解骨髓微环境的作用对于优化AML治疗至关重要.

关键词:

急性骨髓性白血病 (AML) 是一种急性骨髓性白血病.骨髓的 stromal 细胞骨髓的 stromal 细胞细胞循环中的细胞循环.细胞氨酸 (cytarabine) 是一种不同化的差异化差异化.

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