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In this study of 125 patients, these subgroups exhibited distinct molecular profiles:\n                    <jats:italic>KMT2A<\/jats:italic>\n                    -r cases were enriched in RAS pathway mutations, whereas\n                    <jats:italic>KMT2A<\/jats:italic>\n                    -PTD showed a higher burden of epigenetic alterations. Although overall survival (OS) and event-free survival (EFS) did not differ significantly between subgroups, prognosis was strongly influenced by fusion partners.\n                    <jats:italic>MLLT3\/ELL<\/jats:italic>\n                    -rearranged cases showed superior outcomes, but concurrent\n                    <jats:italic>KMT2A<\/jats:italic>\n                    -PTD abrogated this survival advantage,\n                    <jats:italic>AFDN<\/jats:italic>\n                    and other fusions showed poor outcomes. We therefore propose a revised three-tier risk model integrating fusion partner and PTD status, which significantly stratified patient outcomes. The intermediate-risk group (\n                    <jats:italic>MLLT3\/ELL<\/jats:italic>\n                    without PTD) had a 3-year OS of 78.1%, compared to 50.5% in the high-risk group (all PTD), and 34.9% in the very high-risk group (other\n                    <jats:italic>KMT2A<\/jats:italic>\n                    -r) (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.044). For EFS, the rates were 71.0%, 40.1%, and 24.9%, respectively (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.003). Allogeneic hematopoietic cell transplantation significantly improved survival, with 3-year OS rates of 75.2% in transplant recipients versus 22.5% in non-transplanted patients (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001), particularly in high-risk groups and when performed in first complete remission. These findings support the use of molecularly guided, risk-adapted therapy in\n                    <jats:italic>KMT2A<\/jats:italic>\n                    -altered AML.\n                  <\/jats:p>","DOI":"10.1186\/s40164-025-00714-8","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:38:18Z","timestamp":1761043098000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["KMT2A alterations in acute myeloid leukemia: a proposed genetic risk model and transplantation outcomes"],"prefix":"10.1186","volume":"14","author":[{"given":"Li","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianfeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongmei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangqin","family":"Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuhua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kankan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"issue":"5","key":"714_CR1","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1038\/s41375-023-01877-1","volume":"37","author":"C Meyer","year":"2023","unstructured":"Meyer C, Larghero P, Almeida Lopes B, Burmeister T, Groger D, Sutton R, et al. The KMT2A recombinome of acute leukemias in 2023. Leukemia. 2023;37(5):988\u20131005.","journal-title":"Leukemia"},{"issue":"2","key":"714_CR2","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s00277-022-05074-5","volume":"102","author":"J Huang","year":"2023","unstructured":"Huang J, Zhu Y, Li J, Yang G, Zhang S. The KMT2A rearrangement is an early event prior to KMT2A-PTD in AML patients with both molecular aberrations. Ann Hematol. 2023;102(2):495\u20137.","journal-title":"Ann Hematol"},{"issue":"1","key":"714_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/leu.2016.160","volume":"31","author":"QY Sun","year":"2017","unstructured":"Sun QY, Ding LW, Tan KT, Chien W, Mayakonda A, Lin DC, et al. Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD). 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