2025/06/17 by Yoshiaki Usui, Mikiko Endo, Yusuke Iwasaki +4 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Acute Myeloid Leukemia Research #Carcinogens and Genotoxicity Assessment #Acute Lymphoblastic Leukemia research
paper · pdf · doi:10.1158/2643-3230.bcd-24-0355
openalex publication_date 2025/06/17 · openalex created_date 2025/06/18 · openalex updated_date 2026/06/11
Clonal hematopoiesis of indeterminate potential (CHIP) has broad clinical relevance, and TP53 plays various roles within cells. However, the gene-specific and cross-disease significance of CHIP with TP53 mutations (TP53-CHIP) remains unclear. In this study, we evaluated TP53-CHIP using targeted sequencing data of 140,597 individuals without hematologic neoplasms in BioBank Japan. We identified 1,157 individuals with TP53-CHIP and clarified the characteristics of mutations and carriers. TP53-CHIP was associated with poor overall survival, especially because of lymphoid neoplasms and respiratory disease, in addition to myeloid neoplasms. Significant interactions accompanied by excess risks were observed between TP53-CHIP and lifestyle factors for disease-specific mortality: acetaldehyde exposure (resulting from the interaction between drinking and the germline variant of ALDH2) for myeloid neoplasms and smoking for respiratory disease. The clinical significance of TP53-CHIP was sometimes largely independent of variant allele fractions. These findings elucidate aspects of disease pathogenesis and inform personalized risk management. SIGNIFICANCE: TP53-CHIP contributed to a wide range of outcomes besides myeloid neoplasm mortality. TP53-CHIP, when combined with environmental factors, showed a remarkably higher risk for disease-specific mortality, accompanied by excess risks.