荷兰格罗宁根大学Gerwin Huls和荷兰内梅亨大学医学中心Joop H. Jansen共同合作，近期取得重要工作进展。他们研究绘制了3359例普通人群克隆性造血的演化图谱。相关研究成果2023年5月4日在线发表于《癌细胞》杂志上。

据介绍，了解可能驱动恶性进展的克隆性造血作用的演变对于临床决策至关重要。

研究人员通过对来自前瞻性基于人群的生命线队列中3359名个体的7045个连续样本进行错误校正测序，研究了克隆演化的概况，特别关注血细胞增多症和血细胞减少症。剪接体（SRSF2/U2AF1/SF3B1）和JAK2突变克隆在平均3.6年内显示出最高的增长率，而DNMT3A和TP53的克隆大小仅略有增加，与血细胞增多或血细胞减少无关。

然而，在携带相同突变的个体之间观察到巨大的差异，这表明非突变相关因素的调节。克隆扩增不依赖于经典的癌症风险因素（例如吸烟）。发生髓系恶性肿瘤诊断的风险在JAK2、剪接体或TP53突变时最高，而在DNMT3A突变时则不存在，并且大多先于血细胞增多症或血细胞减少症。。

总之，这些结果为高风险演化模式提供了重要的见解，以指导“CHIP”和“CCUS”的监测。

附：英文原文

Title: Evolutionary landscape of clonal hematopoiesis in 3,359 individuals from the general population

Author: Isabelle A. van Zeventer, Aniek O. de Graaf, Jonas B. Salzbrunn, Ilja M. Nolte, Priscilla Kamphuis, Avinash Dinmohamed, Bert A. van der Reijden, Jan Jacob Schuringa, Joop H. Jansen, Gerwin Huls

Issue&Volume: 2023-05-04

Abstract: Knowledge about evolution of clonal hematopoiesis, which may drive malignant progression,is crucial for clinical decision-making. We investigated the landscape of clonal evolutionby error-corrected sequencing on 7,045 sequential samples from 3,359 individuals inthe prospective population-based Lifelines cohort, with a special focus on cytosisand cytopenia. Spliceosome (SRSF2/U2AF1/SF3B1) and JAK2 mutated clones show highest growth rates over a median 3.6-year period, while clonesizes for DNMT3A and TP53 increase only marginally, independent of cytosis or cytopenia. Nevertheless, largedifferences are observed between individuals carrying the same mutation, indicativeof modulation by non-mutation-related factors. Clonal expansion is not dependent onclassical cancer risk factors (e.g., smoking). Risk for incident myeloid malignancydiagnosis is highest for JAK2, spliceosome, or TP53 mutations and absent for DNMT3A, and it is mostly preceded by cytosis or cytopenia. The results provide importantinsight into high-risk evolutionary patterns to guide monitoring of “CHIP” and “CCUS.”

DOI: 10.1016/j.ccell.2023.04.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00132-0