Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Clinical, Mutational, and Transcriptomic Characteristics in Elderly Korean Individuals With Clonal Hematopoiesis Driver Mutations

  • Inki Moon (Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Min Gyu Kong (Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Young Sok Ji (Division of Hematooncology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Se Hyung Kim (Division of Hematooncology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Seong Kyu Park (Division of Hematooncology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Jon Suh (Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Mi-Ae Jang (Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine)
  • Received : 2022.05.20
  • Accepted : 2022.09.29
  • Published : 2023.03.01
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Abstract

Background: 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. Methods: 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. Results: 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 DNMT3A (26 individuals) and TET2 (eight individuals) and were also found in various other genes, including KDM6A, SMC3, TP53, BRAF, PPM1D, SRSF2, STAG1, and ZRSR2. 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. Conclusions: Somatic CHIP driver mutations are common among the elderly in Korea and are detected in various genes, including DNMT3A and TET2. Our study highlights that chronic dysregulation of innate immune signaling is associated with the pathogenesis of various diseases, including hematologic malignancies.

Keywords

Acknowledgement

We appreciate GC Genome and Macrogen for supporting targeted NGS panel and RNA sequencing services, respectively.

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