一种使用二代测序技术对异基因移植后急性髓系白血病克隆进化进行追踪的临床解决方案。
A clinical solution for tracking clonal evolution of acute myeloid leukemia after allogeneic transplantation using bulk next generation sequencing.
作者信息
Krakow Elizabeth F, Lee Nathan, Jenkins Isaac, Sala-Torra Olga, Beppu Lan, Radich Jerald P, Fukuda Bryce, Sandmaier Brenda M, Yeung Cecilia Cs, Bozic Ivana
机构信息
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Division of Hematology-Oncology, University of Washington, Seattle, WA, USA.
出版信息
Bone Marrow Transplant. 2025 May 16. doi: 10.1038/s41409-025-02602-5.
Clinical next generation sequencing (NGS) typically relies on limited gene panels run on bulk marrow or blood. Current computational tools for inferring clonal relationships is generally limited by the use of a small panel of pathogenic mutations to define clones. We developed an online software (CloneTracker) that uses 'incidentally-sequenced' single nucleotide polymorphisms (SNPs) in the regions of recurrent somatic mutations in addition to conventional mutation data from bulk NGS gene panels to provide detailed visualizations of clonal evolution during cancer treatment, alongside clinical data. Tested on 29 patients who underwent non-myeloablative transplantation for AML, CloneTracker successfully reconstructed the evolutionary dynamics of donor engraftment from bulk NGS and rendered intuitive visualizations of residual patient-derived hematopoiesis and relapsing malignant clones. The software does not require sequencing donor samples, as donor-derived clones are identifiable from post-HCT SNP data. This manuscript aims to introduce CloneTracker to the BMT community and make it available for those who would ascertain its clinical utility, e.g, in BMT trials leveraging molecular minimal residual disease (MRD) monitoring and targeted interventions to pre-empt relapse.
临床下一代测序(NGS)通常依赖于对大量骨髓或血液样本进行的有限基因检测。目前用于推断克隆关系的计算工具通常受限于使用一小部分致病突变来定义克隆。我们开发了一款在线软件(CloneTracker),该软件除了利用来自大量NGS基因检测的传统突变数据外,还使用复发性体细胞突变区域中“偶然测序”的单核苷酸多态性(SNP),以结合临床数据详细呈现癌症治疗期间的克隆进化情况。在29例接受非清髓性移植治疗急性髓系白血病(AML)的患者身上进行测试时,CloneTracker成功地从大量NGS数据中重建了供体植入的进化动态,并直观呈现了残留的患者源性造血和复发的恶性克隆。该软件不需要对供体样本进行测序,因为可以从造血干细胞移植后(HCT)的SNP数据中识别出供体来源的克隆。本文旨在向骨髓移植(BMT)领域介绍CloneTracker,并将其提供给那些想要确定其临床效用的人,例如,在利用分子微小残留病(MRD)监测和靶向干预来预防复发的BMT试验中。