Clonal Hematopoiesis in the Era of Precision Medicine: Molecular Mechanisms, Cardiovascular Implications, and Risk of Hematologic Malignancies
DOI:
https://doi.org/10.64784/262Palabras clave:
Clonal hematopoiesis, Clonal hematopoiesis of indeterminate potential, CHIP, Aging, Hematopoietic stem cells, Somatic mutations, Cardiovascular disease, Atherosclerosis, Chronic inflammation, NLRP3 inflammasome, Precision medicine, Hematologic malignancies, Acute myeloid leukemia, Myelodysplastic syndromes, Next-generation sequencing.Resumen
Clonal hematopoiesis has emerged as a major biological process associated with aging and is increasingly recognized as a common mechanistic link between cardiovascular disease and hematologic malignancies. Advances in genomic sequencing have demonstrated that somatic mutations affecting hematopoietic stem cells, particularly in genes involved in epigenetic regulation and DNA repair, promote progressive clonal expansion and persistent inflammatory activation. This review integrates current international evidence regarding the molecular basis, epidemiology, pathophysiological mechanisms, cardiovascular associations, hematologic implications, diagnostic strategies, and emerging therapeutic perspectives of Clonal Hematopoiesis of Indeterminate Potential (CHIP). The available literature consistently indicates that mutations involving DNMT3A, TET2, ASXL1, JAK2, TP53, and PPM1D contribute to chronic immune dysregulation, endothelial dysfunction, accelerated atherosclerosis, and increased susceptibility to myeloid neoplasms. Although most individuals with CHIP remain clinically stable, factors such as larger clone size, multiple driver mutations, persistent cytopenias, and previous exposure to cytotoxic therapy are associated with less favorable outcomes. The evidence also highlights the growing role of next-generation sequencing and precision medicine in identifying individuals at increased cardiovascular and hematologic risk. Despite substantial progress, important challenges remain regarding standardized screening strategies, clinical surveillance, and implementation of mutation-guided management. Continued international collaboration, including broader participation from Latin American research groups, will be essential for improving understanding of clonal hematopoiesis and facilitating the translation of genomic discoveries into personalized clinical practice.
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