Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.
Division of Hematooncology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.
Ann Lab Med. 2023 Mar 1;43(2):145-152. doi: 10.3343/alm.2023.43.2.145. Epub 2022 Oct 25.
Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of blood cells originating from somatically mutated hematopoietic stem cells, is common among the elderly and is associated with an increased risk of hematologic malignancies. We investigated the clinical, mutational, and transcriptomic characteristics in elderly Korean individuals with CHIP mutations.
We investigated CHIP in 90 elderly individuals aged ≥60 years with normal complete blood counts at a tertiary-care hospital in Korea between June 2021 and February 2022. Clinical and laboratory data were prospectively obtained. Targeted next-generation sequencing of 49 myeloid malignancy driver genes and massively parallel RNA sequencing were performed to explore the molecular spectrum and transcriptomic characteristics of CHIP mutations.
We detected 51 mutations in 10 genes in 37 (41%) of the study individuals. CHIP prevalence increased with age. CHIP mutations were observed with high prevalence in (26 individuals) and (eight individuals) and were also found in various other genes, including , and . Baseline characteristics, including age, confounding diseases, and blood cell parameters, showed no significant differences. Using mRNA sequencing, we characterized the altered gene expression profile, implicating neutrophil degranulation and innate immune system dysregulation.
Somatic CHIP driver mutations are common among the elderly in Korea and are detected in various genes, including and . Our study highlights that chronic dysregulation of innate immune signaling is associated with the pathogenesis of various diseases, including hematologic malignancies.
不定潜能的克隆性造血（CHIP）定义为起源于体突变造血干细胞的血细胞存在，在老年人中很常见，并且与血液恶性肿瘤的风险增加相关。我们研究了韩国老年 CHIP 突变个体的临床、突变和转录组特征。
我们在韩国的一家三级保健医院调查了 2021 年 6 月至 2022 年 2 月期间年龄≥60 岁、全血细胞计数正常的 90 名老年个体的 CHIP。前瞻性地获得了临床和实验室数据。对 49 种髓系恶性肿瘤驱动基因进行靶向下一代测序和大规模平行 RNA 测序，以探索 CHIP 突变的分子谱和转录组特征。
我们在 37 名（41%）研究个体的 10 个基因中检测到 51 个突变。CHIP 患病率随年龄增长而增加。CHIP 突变在 （26 名个体）和 （8 名个体）中高发，也存在于其他各种基因中，包括 、 和 。基线特征，包括年龄、并存疾病和血细胞参数，无显著差异。使用 mRNA 测序，我们描述了改变的基因表达谱，暗示中性粒细胞脱颗粒和先天免疫系统失调。
韩国老年人群中存在体细胞 CHIP 驱动突变，在各种基因中均可检测到，包括 、 和 。我们的研究强调，先天免疫信号的慢性失调与各种疾病（包括血液恶性肿瘤）的发病机制有关。
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