美国哈佛医学院Sahand Hormoz等研究人员合作重建出骨髓增生性肿瘤中单个癌细胞的谱系历史和分化轨迹。该项研究成果于2021年2月22日在线发表在《细胞—干细胞》上。
研究人员表示,一些癌症源自单个细胞中的单个突变事件。人们认为,当造血干细胞(HSC)获得驱动基因突变时,被称为骨髓增生性肿瘤(MPN)的血液癌症就开始了。但是,尚不清楚该突变何时首次在个体中发生,以及它如何影响HSC在其天然环境中的行为。
研究人员量化了JAK2-V617F突变对未治疗的MPN个体中HSC自我更新和分化动力学的影响,并使用体细胞突变模式重建了单个HSC的谱系历史。研究人员发现,JAK2-V617F突变发生在MPN诊断之前几十年的单个HSC中,在一个34岁的患者中为9±2岁,在一个63岁的患者中为19±3岁。突变HSC在两个人中都有选择优势。这些结果突出了利用体细胞突变重建癌症谱系的潜力。
附:英文原文
Title: Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Cancer Cells in Myeloproliferative Neoplasms
Author: Debra Van Egeren, Javier Escabi, Maximilian Nguyen, Shichen Liu, Christopher R. Reilly, Sachin Patel, Baransel Kamaz, Maria Kalyva, Daniel J. DeAngelo, Ilene Galinsky, Martha Wadleigh, Eric S. Winer, Marlise R. Luskin, Richard M. Stone, Jacqueline S. Garcia, Gabriela S. Hobbs, Fernando D. Camargo, Franziska Michor, Ann Mullally, Isidro Cortes-Ciriano, Sahand Hormoz
Issue&Volume: 2021-02-22
Abstract: Some cancers originate from a single mutation event in a single cell. Blood cancers known as myeloproliferative neoplasms (MPNs) are thought to originate when a driver mutation is acquired by a hematopoietic stem cell (HSC). However, when the mutation first occurs in individuals and how it affects the behavior of HSCs in their native context is not known. Here we quantified the effect of the JAK2-V617F mutation on the self-renewal and differentiation dynamics of HSCs in treatment-naive individuals with MPNs and reconstructed lineage histories of individual HSCs using somatic mutation patterns. We found that JAK2-V617F mutations occurred in a single HSC several decades before MPN diagnosis—at age 9 ± 2 years in a 34-year-old individual and at age 19 ± 3 years in a 63-year-old individual—and found that mutant HSCs have a selective advantage in both individuals. These results highlight the potential of harnessing somatic mutations to reconstruct cancer lineages.
DOI: 10.1016/j.stem.2021.02.001
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00051-5
Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx