PDF(Pubmed)
Abstract：
Recursive partitioning of healthy consortia led to the development of the Clonal Hematopoiesis Risk Score (CHRS) for clonal haematopoiesis (CH); however, in the practical setting, most cases of CH are diagnosed after patients present with cytopenias or related symptoms. To address this real-world population, we characterize the clinical trajectories of 94 patients with CH and distinguish CH harbouring canonical DNMT3A/TET2/ASXL1 mutations alone (\'sole DTA\') versus all other groups (\'non-sole DTA\'). TET2, rather than DNMT3A, was the most prevalent mutation in the real-world setting. Sole DTA patients did not progress to myeloid neoplasm (MN) in the absence of acquisition of other mutations. Contrastingly, 14 (20.1%) of 67 non-sole DTA patients progressed to MN. CHRS assessment showed a higher frequency of high-risk CH in non-sole DTA (vs. sole DTA) patients and in progressors (vs. non-progressors). RUNX1 mutation conferred the strongest risk for progression to MN (odds ratio [OR] 10.27, 95% CI 2.00-52.69, p = 0.0053). The mean variant allele frequency across all genes was higher in progressors than in non-progressors (36.9% ± 4.62% vs. 24.1% ± 1.67%, p = 0.0064). This analysis in the post-CHRS era underscores the natural history of CH, providing insight into patterns of progression to MN.
摘要：
健康联盟的递归分区导致克隆造血（CH）的克隆造血风险评分（CHRS）的发展；然而，在实际设置中，大多数CH病例是在患者出现血细胞减少症或相关症状后诊断的。为了解决这个现实世界的人口，我们分析了94例CH患者的临床轨迹,并区分了仅有典型DNMT3A/TET2/ASXL1突变的CH(“唯一DTA”)与所有其他组(“非唯一DTA”).TET2，而不是DNMT3A，是现实世界中最普遍的突变。在没有获得其他突变的情况下，单一DTA患者没有进展为髓样肿瘤（MN）。相反，67例非单一DTA患者中有14例（20.1%）进展为MN。CHRS评估显示，非单一DTA中高风险CH的频率更高(vs.唯一的DTA）患者和进展者（vs.非进步者)。RUNX1突变赋予进展为MN的最强风险(比值比[OR]10.27,95%CI2.00-52.69,p=0.0053)。所有基因的平均变异等位基因频率在进展者中高于非进展者(36.9%±4.62%vs.24.1%±1.67%,p=0.0064)。后CHRS时代的这一分析强调了CH的自然历史，提供对MN进展模式的洞察。
