{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:54:31Z","timestamp":1790808871645,"version":"4.1.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"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:sec><jats:title>Background<\/jats:title><jats:p>Therapy-related myeloid neoplasms (t-MN) are aggressive hematologic malignancies with poor prognosis and high-risk clinical features. Recent advances have highlighted the role of molecular data in refining prognostic models. This study aims to analyze a monocentric cohort of t-MN patients, focusing on the clinical and prognostic impact of prior malignancies and their associated molecular landscape.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective analysis was conducted on 61 patients diagnosed with t-MN from an Oncology Hospital and referred to a hematology Unit. Diagnoses were based on established criteria for therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML), with a history of prior exposure to cytotoxic therapy. Cytogenetic and molecular analyses supported the diagnoses. Risk stratification was performed using the revised International Prognostic Scoring System (IPSS-R) and molecular IPSS (IPSS-M) for t-MDS and the 2022 European LeukemiaNet (ELN) classification for t-AML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 61 patients with t-MN were diagnosed: 38 (62.3%) with t-MDS, and 23 (37.7%) with t-AML. The median latency from primary cancer to t-MN diagnosis was 5.8 years (IQR: 2.6\u201312.5). Risk stratification identified 63.2% of t-MDS cases as IPSS-R very-low to intermediate risk, while 57.9% were reclassified as IPSS-M moderate-high to very high risk. Patients with prior hematologic cancer showed a greater tendency toward higher IPSS-R (<jats:italic>p<\/jats:italic>=0.021) and IPSS-M (<jats:italic>p<\/jats:italic>=0.015) risk compared to solid cancer. The IPSS-M, more accurately than R-IPSS, demonstrated predictive value for survival in both univariate and multivariate analyses and effectively predicted leukemic progression in t-MDS. <jats:italic>TP53<\/jats:italic>-mutated cases were more prevalent in patients with prior hematologic cancer (<jats:italic>p<\/jats:italic>=0.043) and associated with longer latency (8.2 years) compared to <jats:italic>TP53<\/jats:italic> wild type (6.1 years, <jats:italic>p<\/jats:italic>=0.044). Allogeneic transplantation proved beneficial, significantly improving survival outcomes in eligible t-MDS and t-AML patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>t-MN exhibits distinct clinical and molecular profiles according to prior malignancy type. Intriguingly, our analysis reveals a distinct latency pattern in <jats:italic>TP53<\/jats:italic>-mutated cases, suggesting unique leukemogenic dynamics. Moreover, IPSS-M proved highly accurate in predicting t-MDS survival. Integrating molecular data into prognostic models enhances risk stratification and informs therapeutic strategies, potentially improving outcomes for t-MN patients. Further studies are needed to validate these findings and refine tailored treatment approaches.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1563990","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:25:24Z","timestamp":1745472324000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Impact of primary cancer history and molecular landscape in therapy-related myeloid 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