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研究揭示自体干细胞移植后造血干细胞的克隆进化
作者:小柯机器人 发布时间:2025/7/2 14:36:41

德克萨斯大学Koichi Takahashi研究组揭示了自体干细胞移植后造血干细胞的克隆进化。2025年7月1日出版的《自然—遗传学》杂志发表了这项成果。

小组对来自10名接受化疗的多发性骨髓瘤患者和6名正常供者的1276个单细胞衍生的造血干细胞和祖细胞(HSPC)集落进行了全基因组测序。美法兰治疗显著增加了突变负担,产生了独特的突变特征,而其他化疗药物的效果微乎其微。因此,治疗后HSPCs的克隆多样性和结构与正常老年人相似,特别是通过低克隆造血的进展,从而表明化疗加速了克隆衰老。对匹配治疗相关髓系肿瘤样本的综合系统发育分析将其克隆起源追溯到多个竞争克隆中的单个HSPC克隆,支持寡克隆向单克隆转化的模型。这些发现强调了对癌症化疗的长期血液学后果进行进一步系统研究的必要性。

据介绍,外源性应激源,如癌症化疗,对正常造血的基因组完整性和克隆动力学的影响还没有很好的定义。

附:英文原文

Title: Clonal evolution of hematopoietic stem cells after autologous stem cell transplantation

Author: Uryu, Hidetaka, Saeki, Koichi, Haeno, Hiroshi, Kapadia, Chiraag Deepak, Furudate, Ken, Nangalia, Jyoti, Spencer Chapman, Michael, Zhao, Li, Hsu, Joanne I., Zhao, Chong, Chen, Shujuan, Tanaka, Tomoyuki, Li, Zongrui, Ogata, Satoko, Hanache, Sarah, Yang, Hui, DiNardo, Courtney, Daver, Naval, Pemmaraju, Naveen, Jain, Nitin, Ravandi, Farhad, Zhang, Jianhua, Song, Xingzhi, Thompson, Erika, Tang, Hongli, Little, Latasha, Gumbs, Curtis, Orlowski, Robert Z., Qazilbash, Muzaffar, Bhalla, Kapil, Colla, Simona, Kantarjian, Hagop, Kanagal-Shamanna, Rashmi, Bueso-Ramos, Carlos, Nakada, Daisuke, Al-Atrash, Gheath, Molldrem, Jeffery, Futreal, P. Andrew, Shpall, Elizabeth, Goodell, Margaret, Garcia-Manero, Guillermo, Takahashi, Koichi

Issue&Volume: 2025-07-01

Abstract: The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal hematopoiesis is not well defined. We conducted whole-genome sequencing on 1,276 single-cell-derived hematopoietic stem and progenitor cell (HSPC) colonies from ten patients with multiple myeloma treated with chemotherapies and six normal donors. Melphalan treatment significantly increased the mutational burden, producing a distinctive mutation signature, whereas other chemotherapeutic agents had minimal effects. Consequently, the clonal diversity and architecture of post-treatment HSPCs resemble those observed in normal elderly individuals, particularly through the progression of oligoclonal hematopoiesis, thereby suggesting that chemotherapy accelerates clonal aging. Integrated phylogenetic analysis of matched therapy-related myeloid neoplasm samples traced their clonal origin to a single-HSPC clone among multiple competing clones, supporting a model of oligoclonal to monoclonal transformation. These findings underscore the need for further systematic research on the long-term hematological consequences of cancer chemotherapy.

DOI: 10.1038/s41588-025-02235-w

Source: https://www.nature.com/articles/s41588-025-02235-w

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex