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在hMSCs中的SLPI过度表达可能与AML中的HSC基因表达特征有关

Pedro L Azevedo¹, Simone Maradei², Ricardo de Sá Bigni³

¹Stem Cell Laboratory, Lab. de Células-Tronco (LCT) Centro, National Cancer Institute (INCA), Praça da Cruz Vermelha 23, 6° andar, Ala C, Rio de Janeiro, RJ, CEP: 20230-130, Brazil. pedro.azevedo01@hotmail.com.

Scientific reports

|July 5, 2024

概括

在急性髓性白血病 (AML) 患者中,改变的骨髓 stromal 细胞释放出更多的分泌白细胞蛋白酶抑制剂 (SLPI). 这种蛋白质影响健康的造血干细胞 (HSC) 的基因表达,可能导致AML的进展.

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:

急性髓性白血病 (AML) 是由造血干细胞 (HSC) 转化为白血病干细胞 (LSC) 引起的.
骨髓 (BM) 微环境,包括介质干细胞 (hMSCs),对于维持HSC至关重要.
在BM利基内的hMSCs的变化可能会影响AML中的HSC行为.

研究的目的:

调查AML患者的hMSCs分泌组 (hMSC-AML) 是否影响HSC基因表达.
识别hMSC-AML分泌体中的特定蛋白质,这些蛋白质可能会影响HSC.
探索这些秘密基因改变对HSCs的功能后果.

主要方法:

来自hMSC-AML和健康的供体HSC (hMSC-HD) 共同培养的分泌体的蛋白质组分析.
从AML患者的hMSC分泌体和BM血中测量分泌白细胞蛋白酶抑制剂 (SLPI) 水平.
在hMSC-AML与hMSC-HD的共同培养后,对HSC的转录组分析.

主要成果:

与健康的HSC共同培养的hMSC-AML的分泌组显示,与hMSC-HD.HD相比,SLPI水平增加.
在AML患者的BM血中也检测到较高的SLPI表达.
与hMSC-AML共同培养的HSCs表现出与细胞周期,增殖和细胞亡相关的基因的改变表达,包括CCNA2,CCNE2,CDK1和CDKN2A的变化.

结论:

改变的hMSC-AML分泌基因组,特别是升高的SLPI,可以改变HSC基因表达.
这些HSC的变化可能涉及与AML发展和进展相关的关键分子机制.
显而易见的是,SLPI是导致AML中HSC利基失调的潜在因素.

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