Racial disparities in clonal hematopoiesis and their impact on hematologic malignancies

Clonal hematopoiesis of indeterminate potential (CHIP) is a known risk factor for hematologic malignancies (HM), but its distribution and clinical implications across diverse ancestries remain poorly characterized. In this study, we investigated CHIP and its progression to HM in a large, racially diverse cohort from the All of Us Research Program, comprising 245,388 participants. We identified 10,446 CHIP driver mutations in 9,476 individuals. Our analysis revealed clear racial disparities in CHIP prevalence and mutational profiles: African American (AA) individuals had higher odds of CHIP and exhibited distinct mutation patterns compared to White American (WA) individuals. Consistent with prior studies, CHIP was associated with an increased risk of HM, particularly myeloid malignancies. Notably, ancestry influenced the subtype of myeloid malignancy observed; CHIP was more strongly linked to myeloproliferative neoplasms in AA individuals compared with WA individuals. These findings demonstrated significant racial differences in CHIP biology and HM progression, highlighting the need for ancestry-informed approaches to CHIP risk assessment and HM prevention.