[Clonal hematopoiesis and myeloid neoplasms: from molecular basis to clinical implications]

Clonal hematopoiesis (CH) refers to the age-associated expansion of hematopoietic stem cell clones carrying somatic mutations that are commonly observed in myeloid malignancies. With the widespread use of next-generation sequencing, such mutations are now frequently detected even in individuals without overt hematologic abnormalities. CH in the absence of cytopenia or hematologic malignancy is defined as clonal hematopoiesis of indeterminate potential (CHIP), whereas CH accompanied by unexplained cytopenia is classified as clonal cytopenia of undetermined significance (CCUS), a recognized pre-malignant condition with a high risk of progression to myeloid neoplasms. The molecular landscape of CH is dominated by mutations in epigenetic regulators such as DNMT3A, TET2, and ASXL1, although spliceosome genes, signaling molecules, and DNA damage-response genes are also involved. Clonal expansion and malignant transformation are shaped by selective pressures including aging, chronic inflammation, and therapy-related DNA damage. Progression risk varies widely depending on mutation type, variant allele frequency, and clonal complexity, and several predictive models have been proposed. Beyond hematologic malignancies, CH has also been linked to cardiovascular and inflammatory diseases, highlighting its broader clinical relevance and the need for risk-adapted clinical strategies.