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Evolving nomenclature and shifting classification criteria make correct recognition essential. Recent work integrating clonal hematopoiesis and germline variants clarifies mechanisms that drive driver mutations, and this review addresses clinical and biological definitions, mechanistic advances, and prevention and management challenges.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/therapy-related-myeloid-neoplasm-biology-and-mechanistic-aspects-of-malignant-progression/341227/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/therapy-related-myeloid-neoplasm-biology-and-mechanistic-aspects-of-malignant-progression/341227.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What are therapy-related myeloid neoplasms (t-MN)?","Question",{"text":113,"@type":114},"t-MN are myeloid malignancies that arise after a history of chemo/radiotherapy given for an unrelated condition.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How are t-MN characterized clinically and biologically?",{"text":118,"@type":114},"They are associated with specific genetic signatures, aggressive disease features, and a dismal prognosis, with classification and nomenclature evolving over time.",{"name":120,"@type":111,"acceptedAnswer":121},"What mechanisms are discussed as drivers of malignant progression in t-MN?",{"text":122,"@type":114},"The review highlights complex interactions including aging, inflammation, inherited genetic susceptibility, and clonal selection of pre-existing resistant clones, further informed by clonal hematopoiesis and germline variants.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},341227,1790382086,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","biomedicines  \nReview  \nTherapy-Related Myeloid Neoplasm: Biology and Mechanistic Aspects of Malignant Progression  \nSerena Travaglini 1,2, Massimiliano Marinoni 2, Valeria Visconte 3 and Luca Guarnera 2, *  \nCitation: Travaglini, S.; Marinoni, M.; Visconte, V.; Guarnera, L. TherapyRelated Myeloid Neoplasm: Biology and Mechanistic Aspects of Malignant Progression. Biomedicines 2024, 12, 1054. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biomedicines12051054  \nAcademic Editor: Michele Gottardi  \nReceived: 1 April 2024  \nRevised: 2 May 2024  \nAccepted: 7 May 2024  \nPublished: 10 May 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy  \n2 Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy  \n3 Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA  \n* Correspondence: lucaguarnera@live.com or guarnel@ccf.org  \nAbstract: Therapy-related myeloid neoplasms (t-MN) arise after a documented history of chemo/ radiotherapy as treatment for an unrelated condition and account for 10–20% of myelodysplastic syndromes and acute myeloid leukemia. T-MN are characterized by a specific genetic signature, aggressive features and dismal prognosis. The nomenclature and the subsets of these conditions have changed frequently over time, and despite the fact that, in the last classification, they lost their autonomous entity status and became disease qualifiers, the recognition of this feature remains of major importance. Furthermore, in recent years, extensive studies focusing on clonal hematopoiesisand germline variants shed light on the mechanisms of positive pressure underpinning the rise of driver gene mutations in t-MN. In this manuscript, we aim to review the evolution of defining criteria and characteristics of t-MN from a clinical and biological perspective, the advances in mechanistic aspects of malignant progression and the challenges in prevention and management.  \nKeywords: Therapy-related Myeloid Neoplasm; t-MN; Myeloid Neoplasm post cytotoxic therapy; MN-pCT  \n1. Introduction  \nTherapy-related myeloid neoplasms (t-MN) are a subgroup of myeloid malignancies, including myelodysplastic syndromes (MDS), MDS/myeloproliferative neoplasms (MDS/MPN) and acute myeloid leukemia (AML) arising from non-correlated conditions treated with cytotoxic therapies. Advances over the years led to an increase in diagnosesand better response rates in solid tumors and autoimmune conditions, making long-term complications, such as t-MN, an increasing issue [1,2] .  \nt-MN accounts for 10–20% of all MDS/AML, and the risk of onset in patients undergoing cytotoxic therapy ranges from 1 to 10%, depending on the type of cancer and treatment, representing one of the worst long-term side effects [3–5] . Particularly, primary tumors, lymphoid malignancies and gynecologic cancers are the most common types of tumors, with a 4.7-fold increased risk compared to the general population, as reported by Morton et al. [4] .  \nt-MN, in fact, arises more commonly in older patients, carrying multiple comorbidities and with lower fitness, and unlikely to undergo intensive treatments [6] .  \nFurthermore, the inherent features of the disease, characterized by high-risk cytogenetics and molecular alterations, make the management of t-MN a challenge for the physician [7–9] .  \nThus, both disease-related and patient-related features explain the lower response rate of t-MN, when compared to de novo MN, and the poor prognosis, standing at \u003C10% at 5","cbCaig2eqkhXKeHH","https://ap.wps.com/l/cbCaig2eqkhXKeHH","pdf",1481795,18,"English","# Abstract\n# Introduction\n# Pathophysiology\n## Germline Predisposition","[{\"question\":\"What are therapy-related myeloid neoplasms (t-MN)?\",\"answer\":\"t-MN are myeloid malignancies that arise after a history of chemo/radiotherapy given for an unrelated condition.\"},{\"question\":\"How are t-MN characterized clinically and biologically?\",\"answer\":\"They are associated with specific genetic signatures, aggressive disease features, and a dismal prognosis, with classification and nomenclature evolving over time.\"},{\"question\":\"What mechanisms are discussed as drivers of malignant progression in t-MN?\",\"answer\":\"The review highlights complex interactions including aging, inflammation, inherited genetic susceptibility, and clonal selection of pre-existing resistant clones, further informed by clonal hematopoiesis and germline variants.\"}]","Therapy-Related Myeloid Neoplasm - Biology and Mechanistic Aspects of Malignant Progression | PDF",1790041040,45]