{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:56:34Z","timestamp":1790772994896,"version":"4.1.0"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Therapy-related myeloid neoplasms (t-MNs), which develop following cytotoxic chemotherapy or radiotherapy, remain one of the most significant clinical challenges in modern hematology due to their aggressive clinical course and poor survival outcomes. The traditional paradigm regarded the development of t-MNs as a consequence of\n                    <jats:italic>de novo<\/jats:italic>\n                    genetic damage induced by anticancer therapies. However, recent data concerning genomics and clonal evolution have fundamentally transformed our understanding of the biological origins of the disease. Current evidence demonstrates that low-level, clinically silent hematopoietic clones are present in the peripheral blood or bone marrow years prior to disease onset in a substantial proportion of t-MN cases. The pathogenesis of t-MNs is therefore being reconceptualized, not merely as the emergence of\n                    <jats:italic>de novo<\/jats:italic>\n                    treatment-induced mutations, but rather as the expansion and progression to malignant transformation of pre-existing silent clones under selective pressure. Clonal hematopoiesis (CH) is a dynamic biological process characterized by the acquisition of a proliferative advantage by specific cell populations, resulting from somatic mutations accumulated by hematopoietic stem cells (HSCs) throughout life. A clinically defined subgroup of this process, including CH of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS), are defined as the presence of somatic mutations with a variant allele frequency (VAF) of \u22652% in genes associated with myeloid malignancies. Both are recognized as clinically meaningful pre-cancerous states, differentiated primarily by the presence of unexplained cytopenias in CCUS. The presence of CH by itself is insufficient to drive malignant transformation. The observation that only a small fraction of individuals harboring CHIP or CCUS ultimately develop myeloid neoplasia indicates that clonal progression is not solely dictated by the presence of a mutation, but rather by the biological characteristics of the clone, the specific mutation type, clone size, environmental stressors, and the bone marrow microenvironment. The fundamental paradigm has thus shifted from simply asking \u201cwhich patients have CH?\u201d to determining \u201cwhich silent clones possess the potential to evolve into aggressive myeloid neoplasms in the future?\u201d The concept of the \u201cpower of silent clones\u201d provides a novel biological perspective in t-MN risk stratification, establishing a foundational framework for the future development of personalized surveillance, early intervention, and targeted preventative strategies. Deciphering CH enables precise risk stratification and helps intercept myeloid malignancies before clinical onset.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1943135","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:55:07Z","timestamp":1790769307000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Silent, but not innocent: the emerging role of clonal hematopoiesis in predicting therapy-related myeloid neoplasms"],"prefix":"10.3389","volume":"16","author":[{"given":"\u015eerife","family":"Emre \u00dcnsal","sequence":"first","affiliation":[{"name":"Department of Hematology, Faculty of Medicine, Erciyes University","place":["Kayseri, 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