自体干细胞移植后造血干细胞的克隆进化

IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY
Hidetaka Uryu, Koichi Saeki, Hiroshi Haeno, Chiraag Deepak Kapadia, Ken Furudate, Jyoti Nangalia, Michael Spencer Chapman, Li Zhao, Joanne I. Hsu, Chong Zhao, Shujuan Chen, Tomoyuki Tanaka, Zongrui Li, Satoko Ogata, Sarah Hanache, Hui Yang, Courtney DiNardo, Naval Daver, Naveen Pemmaraju, Nitin Jain, Farhad Ravandi, Jianhua Zhang, Xingzhi Song, Erika Thompson, Hongli Tang, Latasha Little, Curtis Gumbs, Robert Z. Orlowski, Muzaffar Qazilbash, Kapil Bhalla, Simona Colla, Hagop Kantarjian, Rashmi Kanagal-Shamanna, Carlos Bueso-Ramos, Daisuke Nakada, Gheath Al-Atrash, Jeffery Molldrem, P. Andrew Futreal, Elizabeth Shpall, Margaret Goodell, Guillermo Garcia-Manero, Koichi Takahashi
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引用次数: 0

摘要

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。我们对来自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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Clonal evolution of hematopoietic stem cells after autologous stem cell transplantation

Clonal evolution of hematopoietic stem cells after autologous stem cell transplantation

Clonal evolution of hematopoietic stem cells after autologous stem cell transplantation
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. Analysis of whole-genome sequencing data from hematopoietic stem and progenitor cells taken from patients with myeloma shows how treatment shapes clonal architecture and sheds light on the evolution of treatment-related myeloid neoplasms.
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来源期刊
Nature genetics
Nature genetics 生物-遗传学
CiteScore
43.00
自引率
2.60%
发文量
241
审稿时长
3 months
期刊介绍: Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human and plant traits and on other model organisms. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation. Integrative genetic topics comprise, but are not limited to: -Genes in the pathology of human disease -Molecular analysis of simple and complex genetic traits -Cancer genetics -Agricultural genomics -Developmental genetics -Regulatory variation in gene expression -Strategies and technologies for extracting function from genomic data -Pharmacological genomics -Genome evolution
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