{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:31:24Z","timestamp":1786469484095,"version":"build-2736575974"},"reference-count":87,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Italiano per la Scienza","award":["FIS-2024-06156"],"award-info":[{"award-number":["FIS-2024-06156"]}]},{"name":"\u201cAmici di Beat Leukemia Dr. Alessandro Cevenini\u201d\u2014ONLUS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Fms-related receptor tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations occur in approximately 20\u201325% of patients with acute myeloid leukemia (AML) and are associated with increased relapse risk and inferior survival outcomes. Although measurable residual disease (MRD) has become a key prognostic tool for guiding post-remission treatment decisions, FLT3-ITD was historically considered a suboptimal MRD marker because of its subclonal nature, structural heterogeneity and dynamic behavior during disease evolution. In addition, FLT3-ITD has not yet been fully integrated into routine MRD monitoring due to methodological limitations and a lack of standardized workflows. The latest European LeukemiaNet (ELN)-DAVID 2025 recommendations stressed the use of ultra-high sensitivity (UHS) next-generation sequencing (NGS) technologies to detect FLT3-ITD MRD with improved precision, enabling reliable longitudinal tracking of patient-specific clones at very low variant allele frequencies (VAF). Indeed, despite prospective evidence supporting this approach remaining limited, FLT3-ITD-based MRD monitoring is emerging as a clinically relevant prognostic indicator, contributing to the identification of patients at increased risk of relapse and refining risk stratification, while also informing therapeutic decision-making, particularly in the peri-transplant setting. The present review summarizes the biological underpinnings of FLT3-ITD mutated (FLT3-ITDmut) AML, discusses the methodological challenges of MRD detection, and critically evaluates the evolving role of MRD in refining relapse prediction, supporting post-remission therapy tailoring, and contributing to a harmonized framework for FLT3-ITDmut AML management.<\/jats:p>","DOI":"10.3390\/cancers18162586","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:30:32Z","timestamp":1786465832000},"page":"2586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FLT3-ITD Measurable Residual Disease in Acute Myeloid Leukemia: Implications for FLT3 Inhibitor-Based Therapies"],"prefix":"10.3390","volume":"18","author":[{"given":"Giorgia","family":"Silvestrini","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5411-1502","authenticated-orcid":false,"given":"Serena","family":"Travaglini","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Guarnera","sequence":"additional","affiliation":[{"name":"PhD Program in Immunology, Molecular Medicine and Applied Biotechnology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Lelli","sequence":"additional","affiliation":[{"name":"PhD Program in Immunology, Molecular Medicine and Applied Biotechnology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariadomenica","family":"Divona","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Casciani","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ceccolini","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7699-1427","authenticated-orcid":false,"given":"Giulia","family":"Falconi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1936-3592","authenticated-orcid":false,"given":"Tiziana","family":"Ottone","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Neuro-Oncohematology Unit, Santa Lucia Foundation, Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.), 00143 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-4761","authenticated-orcid":false,"given":"Maria Teresa","family":"Voso","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Neuro-Oncohematology Unit, Santa Lucia Foundation, Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.), 00143 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1056\/NEJM199909303411407","article-title":"Acute Myeloid Leukemia","volume":"341","author":"Lowenberg","year":"1999","journal-title":"N. 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