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对克隆型B淋巴细胞作为血细胞癌症的储存体的遗传证据

Carmen González¹, Juan-Jose Garces², Hector Gracia³

¹Cancer Center Clinica Universidad de Navarra (CCUN) , Centro de Investigacion Medica Aplicada, Universidad de Navarra (CIMA), IDISNA, CIBER-ONC CB16/12/00369 and CB16/12/00489 Pamplona Spain.

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概括

多发性骨髓瘤和轻链氨基粉症起源于恶性血细胞,而不是早期的B细胞. 克隆型B细胞是新生前的前体细胞,很少影响疾病的进展.

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) 和轻链氨基粉症 (AL) 的细胞起源受到争议.
血细胞 (PC) 和早期B细胞起源之间的区别影响了诊断和治疗.
了解驱动突变的B细胞发育阶段至关重要.

研究的目的:

确定B细胞发育阶段,其中包含MM和AL的驱动基因变异.
澄清克隆型B细胞在MM和AL病原发生中的作用.
调查克隆型B细胞对最小残留疾病评估的影响.

主要方法:

纯化的MM和AL样本的单细胞和外基因组测序.
在B细胞前体和成熟B细胞中检测克隆型B细胞受体 (BCR).
配对单细胞转录组分析以确认细胞表型.

主要成果:

克隆型B细胞受体在MM和AL患者的B细胞前体和成熟B细胞的一小部分 (≤0.4%) 中被发现.
驱动基因变异主要在瘤血细胞中被发现,在不成熟的B细胞阶段很少发生.
克隆型B细胞可能会通过BCR测序导致错误的阳性最小残留疾病评估.

结论:

克隆型B细胞代表MM和AL中恶性血细胞的前新生体前体.
这些前体细胞不太可能参与疾病的积极进展.
主要驱动突变存在于终端分化的血细胞中,而不是早期的B细胞阶段.

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