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来自BM-MSCs的MMP14通过JAK/STAT通路促进急性髓性白血病的进展和Ara-C耐药性

Jinxian Wu¹, Xinqi Li¹, Yin Liu¹

¹Department of Hematology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430072, P. R. China.

Experimental hematology & oncology

|March 23, 2025

概括

介酶体 stromal 细胞 (MSCs) 通过MMP14促进急性髓性白血病 (AML) 的生长和化学抵抗. 在MSC中抑制MMP14可以通过破坏这一关键的交叉声交响来提供新的AML疗法.

科学领域:

血液学血液学血液学
癌症生物学癌症生物学
干细胞生物学干细胞生物学

背景情况:

白血病干细胞 (LSCs) 和介酶体 stromal 细胞 (MSCs) 之间的交叉影响白血病的进展和治疗结果.
在急性髓性白血病 (AML) 中,MSC衍生的矩阵金属蛋白酶-14 (MMP14) 的特定作用仍然在很大程度上未被探索.

研究的目的:

调查MSC衍生的MMP14在AML发病,进展和化学抵抗中的作用.
阐明MSCs,特别是通过MMP14影响AML行为的机制.

主要方法:

对抗AML患者衍生的MSCs (AML-MSCs) 和健康的供体衍生的MSCs (HD-MSCs) 的比较.
基因和蛋白质表达的分析.
在MSC中击倒MMP14.
用AML细胞进行体外共同培养测定.
在体内白血病发生模型.
涉及PGE2分泌和JAK-STAT通路激活的机制研究.
对细胞氨酸 (Ara-C) 的化学疗法耐药性的评估.

主要成果:

与HD-MSC相比,AML-MSC显示出对AML细胞生长的增强支持.
在MSC中MMP14的敲击损害了MSC的增殖和干性.
MSCs抑制了AML细胞的增殖和细胞循环,增加了细胞亡,从而减少了白血病的潜力.
通过PGE2和JAK-STAT激活,MMP14调解了肌肉结构的改变,促进了白血病的进展.
抑制MMP14可以降低AML细胞中MSC诱导的化学抵抗.

结论:

来自MSC的MMP14极大地促进了AML的进展和化学抵抗.
准MMP14信号通路为AML提供了一个潜在的新疗法策略.

关键词:

急性骨髓性白血病 (AML) 是一种急性骨髓性白血病.在JAK/STAT路径中.在MMP14中,MMP14是MMP14中的一个.介质细胞层细胞是介质细胞层细胞.在PGE2的基础上,PGE2

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