Single-cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia.
Single-cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia.
复制标题
急性髓系白血病可测量残留疾病的单细胞基因型和表型分析。
DOI：
10.1126/sciadv.adg0488
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发表时间：
2023
期刊：
影响因子：
13.6
通讯作者：
Roshal,Mikhai
中科院分区：
文献类型：
--
作者：
Robinson,TroyM;Bowman,RobertL;Persaud,Sonali;Liu,Ying;Neigenfind,Rosemary;Gao,Qi;Zhang,Jingping;Sun,Xiaotian;Miles,LindeA;Cai,ShengF;Sciambi,Adam;Llanso,Aaron;Famulare,Christopher;Goldberg,Aaron;Dogan,Ahmet;Roshal,Mikhai
可测量残留病（MRD）定义为治疗后持续存在的癌细胞群，是急性髓性白血病和其他恶性肿瘤疾病复发的关键储库。了解使MRD克隆能够抵抗治疗的生物学对于指导更有效的治愈性治疗的发展是必要的。区分残留白血病克隆、白血病前期克隆和正常前体仍然是当前MRD工具的挑战。在这里，我们开发了一个单细胞MRD（scMRD）检测结合流式细胞仪富集的目标前体/原始细胞群体与集成的单细胞DNA测序和免疫分型。我们的scMRD检测显示出约0.01%的高灵敏度，解卷积克隆结构，并提供克隆特异性免疫表型数据。总之，我们的scMRD测定增强了MRD检测，同时阐明了急性髓性白血病治疗后存活的克隆造血/白血病前期和白血病细胞的克隆结构。
Measurable residual disease (MRD), defined as the population of cancer cells that persist following therapy, serves as the critical reservoir for disease relapse in acute myeloid leukemia and other malignancies. Understanding the biology enabling MRD clones to resist therapy is necessary to guide the development of more effective curative treatments. Discriminating between residual leukemic clones, preleukemic clones, and normal precursors remains a challenge with current MRD tools. Here, we developed a single-cell MRD (scMRD) assay by combining flow cytometric enrichment of the targeted precursor/blast population with integrated single-cell DNA sequencing and immunophenotyping. Our scMRD assay shows high sensitivity of approximately 0.01%, deconvolutes clonal architecture, and provides clone-specific immunophenotypic data. In summary, our scMRD assay enhances MRD detection and simultaneously illuminates the clonal architecture of clonal hematopoiesis/preleukemic and leukemic cells surviving acute myeloid leukemia therapy.