Clonal Hematopoiesis in Colorectal Cancer: Mechanisms and Implications

Clonal hematopoiesis (CH) arises from the expansion of hematopoietic stem and progenitor cells bearing somatic mutations, often in genes linked to epigenetic regulation and inflammation. Once considered a benign age-related phenomenon, CH has gained increasing attention for its potential to influence cancer biology beyond hematologic malignancies. Recent studies have uncovered an unexpectedly high prevalence of CH in patients with colorectal cancer (CRC), raising important questions about its origin, context-specific drivers, and pathological consequences. While cytotoxic therapies are known contributors, accumulating evidence suggests that the chronic inflammatory and metabolic alterations intrinsic to CRC may also shape hematopoietic clonality. In turn, CH-derived myeloid cells harboring mutations such as DNMT3A or TET2 can modulate the tumor microenvironment, promote inflammation, and impair antitumor immunity. In this review, we synthesize emerging findings on the bidirectional relationship between CH and CRC, highlighting the mechanistic underpinnings and potential implications for disease progression, therapeutic resistance, and immune modulation. Understanding this evolving interface may open new avenues for risk stratification and treatment personalization in CRC.