针对多发性骨髓瘤的起源,沿着造血干细胞淋巴细胞分化系的分化线路向多发性骨髓瘤
Jiaojiao Guo1,2, Yaru Li3, Zhiling Yan4
1State Key Laboratory of Experimental Hematology, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, National Clinical Research Center for Geriatric Disorders, FuRong Laboratory, Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China.
Science translational medicine
|November 19, 2025
概括
多发性骨髓瘤从具有染色体1q放大特异性的B细胞开始,由FCRL5.5驱动. 针对这些细胞进行FCRL5 CAR T治疗对复发性或耐药性多发性髓瘤患者有希望.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
背景情况:
- 多发性骨髓瘤 (MM) 的发病包括MM发起细胞 (MIC) 中复杂的恶性转化机制.
- 识别驱动基因和异常分化阶段对于理解MM的开始和进展至关重要.
研究的目的:
- 识别导致多发性骨髓瘤恶性转变的遗传事件和细胞起源.
- 研究染色体1q放大 (1qAmp) 和FCRL5在MM发育中的作用.
- 评估针对复发性或耐火性MM (RRMM) 的FCRL5的治疗潜力.
主要方法:
- 单细胞测序和遗传痕迹分析跨血造干细胞到淋巴细胞系差异化.
- 在体外和体内实验中评估1qAmp对B细胞转化的影响.
- 对FCRL5与IRF4/SPI1复合体相互作用的分析.
- 在RRMM患者中对FCRL5 CAR T细胞的临床评估.
主要成果:
- 染色体1qAmp起源于CD24-FCRL5+ B细胞亚组,开始恶性血细胞的转化.
- 1qAmp增强了B细胞的增殖,并促进了血细胞的分化.
- FCRL5通过IRF4/SPI1复合体促进恶性血细胞的分化.
- 在RRMM患者中,FCRL5 CAR T细胞疗法证明了安全性和有效性.
结论:
- 遗传事件,特别是特定B细胞子集中的1qAmp,与MM启动和恶性转变有关.
- FCRL5在驱动MM进展方面发挥着关键作用,并代表着潜在的治疗点.
- 针对MIC及其瘤基因,例如通过FCRL5 CAR T细胞,为新型RRMM疗法提供了基础.
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