功能和分子分析显示,在多发性髓瘤患者的诱导后,HSPCs受损
Thanh Mai Baumhardt1, Amanda Amoah2, Markus Hoenicka3
1Department of Internal Medicine III, University Hospital of Ulm, 89081 Ulm, Germany.
Stem cells translational medicine
|November 19, 2025
概括
治疗多发性骨髓瘤 (MM) 患者的造血干细胞和原始细胞 (HSPC) 显示功能受损和高风险特征. 改善自身干细胞移植 (ASCT) 结果可能涉及净化HSPC以去除这些改变的细胞.
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:
- 高剂量化疗和自身干细胞移植 (ASCT) 是可移植多发性骨髓瘤 (MM) 患者的标准.
- 尽管ASCT,患者面临复发和治疗并发症的重大风险.
- 了解MM中的造血干细胞和原生细胞 (HSPC) 功能对于改善ASCT结果至关重要.
研究的目的:
- 从功能上分析新诊断的 (NDMM) 和化疗治疗的MM患者的HSPC.
- 通过异种移植和单细胞测序来研究诱导治疗对HSPC潜力的影响.
- 确定改善MM患者ASCT结果的新策略.
主要方法:
- 在异种移植模型中对NDMM和接受治疗的MM患者的HSPC的功能评估.
- 对CD34+HSPC进行深入的单细胞RNA测序分析.
- 在MM患者和健康捐赠者之间对HSPC潜力和转录资料的比较.
主要成果:
- 与对照组相比,接受治疗的MM患者的HSPC显示出显著受损的复制潜力和降低的B细胞产量.
- 接受治疗的MM患者的CD34+HSPC在治疗后获得了高风险的MM表达特征.
- 这种特征主要位于颗粒细胞/巨细胞原始体 (GMPs),大核细胞红色素原始体 (MEPs) 和单细胞中,节省了造血干细胞 (HSCs).
结论:
- 在MM患者的HSPC中,化学疗法诱导的转录失调,特别是在髓质前体和单细胞中,可能会导致复发风险.
- 净化HSPC收获以消除这些改变的骨髓原生细胞和单细胞可以提高ASCT的疗效.
- 准这些失调的细胞群可能是改善多发性髓瘤移植结果的新策略.
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