Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased risk of several chronic diseases. However, gene-specific CHIP implications remain to be characterized. Usui and colleagues conducted an epidemiologic evaluation of 140,597 individuals in BioBank Japan, including 1,157 cases with CHIP in TP53 gene (TP53-CHIP) identified by high-coverage sequence data. In this largest-to-date cohort followed over a decade, TP53-CHIP associated with myeloid and lymphoid neoplasms, and respiratory disease mortality. The impact of TP53-CHIP was modulated by an interplay of host and environmental factors. For example, alcohol consumption in TP53-CHIP carriers conferred higher risk of liver disease only in the presence of a genetic variant in an alcohol-metabolizing enzyme. These findings elucidate TP53-CHIP’s role in disease pathogenesis and its potential to inform personalized risk management.

See article, p. 298.

The differentiation landscape of an acute myeloid leukemia (AML) patient reflects key biological properties...

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