{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:14:31Z","timestamp":1791224071116,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002618","name":"AAMDSIF","doi-asserted-by":"crossref","award":["JR22\/00041"],"award-info":[{"award-number":["JR22\/00041"]}],"id":[{"id":"10.13039\/100002618","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Instituto of de Salud Carlos III","award":["JR22\/00041"],"award-info":[{"award-number":["JR22\/00041"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>KMT2A (alias: mixed-lineage leukemia [MLL]) gene mapping on chromosome 11q23 encodes the lysine-specific histone N-methyltransferase 2A and promotes transcription by inducing an open chromatin conformation. Numerous genomic breakpoints within the KMT2A gene have been reported in young children and adults with hematologic disorders and are present in up to 10% of acute leukemias. These rearrangements describe distinct features and worse prognosis depending on the fusion partner, characterized by chemotherapy resistance and high rates of relapse, with a progression-free survival of 30\u201340% and overall survival below 25%. Less intensive regimens are used in pediatric patients, while new combination therapies and targeted immunotherapeutic agents are being explored in adults. Beneficial therapeutic effects, and even cure, can be reached with hematopoietic stem cell transplantation, mainly in young children with dismal molecular lesions; however, delayed related toxicities represent a concern. Herein, we summarize the translocation partner genes and partial tandem duplications of the KMT2A gene, their molecular impact, clinical aspects, and novel targeted therapies.<\/jats:p>","DOI":"10.3390\/ijms25169023","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T09:13:48Z","timestamp":1724145228000},"page":"9023","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["KMT2A Rearrangements in Leukemias: Molecular Aspects and Therapeutic Perspectives"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-0663","authenticated-orcid":false,"given":"Luca","family":"Guarnera","sequence":"first","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44114, USA"},{"name":"Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1584-1780","authenticated-orcid":false,"given":"Matteo","family":"D\u2019Addona","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-7847","authenticated-orcid":false,"given":"Carlos","family":"Bravo-Perez","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44114, USA"},{"name":"Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer, CIBERER\u2014Instituto de Salud Carlos III, University of Murcia, IMIB-Pascual Parrilla, 30005 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-1509","authenticated-orcid":false,"given":"Valeria","family":"Visconte","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/s41375-023-01877-1","article-title":"The KMT2A recombinome of acute leukemias in 2023","volume":"37","author":"Meyer","year":"2023","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"G\u00f3recki, M., Kozio\u0142, I., Kopystecka, A., Budzy\u0144ska, J., Zawitkowska, J., and Lejman, M. 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