Germline Genetics, Disease, and Exposure to Medication Influence Longitudinal Dynamics of Clonal Hematopoiesis

Details

• Personal Author:
  Bejan CA ; Bick AG ; Ferrell PB ; Heimlich JB ; Jones A ; Kishtagari A ; Li Y ; Luo LY ; Mack T ; Mickels NA ; Pershad Y ; Savona MR ; Silver AJ ; Ulloa J ; Van Amburg JC ; Vlasschaert C ; Xu Y
• Description:
  Clonal hematopoiesis of indeterminate potential (CHIP) occurs when a hematopoietic stem cell acquires a somatic driver mutation in a leukemia-associated gene, with a variant allele fraction (VAF) exceeding 2% in peripheral blood. Higher VAF is associated with increased morbidity and mortality risk. Identifying factors influencing clonal expansion rate is crucial for risk stratification in CHIP patients. Recent cost-effective targeted assays have enabled serial sequencing and longitudinal profiling of CHIP dynamics. We present the largest longitudinal analysis of CHIP mutational dynamics to-date, examining 3,000 individuals from the Vanderbilt BioVU biobank. Our findings reveal that CHIP growth rates vary significantly by driver gene and are influenced by germline variants and medication exposures. Additionally, we demonstrate that monitoring blood counts may be more informative for risk stratification than frequent resequencing in CHIP patients. [Description provided by NIOSH]
• Subjects:
  Genetics Hematologic Tests Occupational Health Safety
• Keywords:
  Gene Mutation Genes Germ Cells Hematology Hematopoiesis Longitudinal Study
• ISSN:
  1592-8721
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Birmingham Region [OSHA] ; New York ; New York City Region [OSHA] ; Tennessee
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  110
• Issue:
  4
• NIOSHTIC Number:
  nn:20070830
• Citation:
  Haematologica 2025 Apr; 110(4):1010-1018
• Email:
  alexander.bick@vumc.org
• Federal Fiscal Year:
  2025
• Performing Organization:
  Albert Einstein College of Medicine, Bronx, New York
• Peer Reviewed:
  False
• Start Date:
  20210701
• Source Full Name:
  Haematologica
• End Date:
  20240630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ed644849cf01bfdf1d701330589c77ca0897bfbdb1ad83d384db1ed21c37cb8a829d539f458e63c6c3b235d6cdfaf026a1e83ebd73f07ca7b026cdf6ebe26c5f
• Download URL:
  https://stacks.cdc.gov/view/cdc/208978/cdc_208978_DS1.pdf
• File Type:
  [PDF - 1.48 MB ]