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This study explored the role of static and dynamic profiles of mutational clonal burden to predict outcomes by analyzing marrow samples from 228 VEN\u2009+\u2009AZA treated AML cases at \u201cPre-treatment\u201d (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009228), \u201cBest-response\u201d (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009105), and \u201cRelapse\u201d (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200927) phases using targeted-capture sequencing. In a multivariate model, older age, prior AZA,\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation with variant allele frequency \u22650.10, and RAS-pathway mutations predicted shorter overall survival (OS), while\n                    <jats:italic>BCORL1<\/jats:italic>\n                    mutation predicted longer OS. Notably, myelodysplasia-related gene mutations, which constitute adverse factors in ELN 2022, predicted favorable survival. Achieving composite complete remission (CRc) significantly predicted longer OS (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) but showed residual mutations in 76.2% of the cases. Among CRc cases, relapse-free survival was stratified by molecular clearance of mutations other than\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    ,\n                    <jats:italic>ASXL1<\/jats:italic>\n                    , and\n                    <jats:italic>TET2<\/jats:italic>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.04). In addition, 37% of relapsed cases showed a change of major clones, with 40% having potential targets of molecular-targeting treatment. This study revealed the novel prognostic role of myelodysplasia-related gene mutations and established the importance of molecular response assessment in CRc phase.\n                  <\/jats:p>","DOI":"10.1038\/s41375-025-02625-3","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T15:05:31Z","timestamp":1745247931000},"page":"1362-1367","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Impact of myelodysplasia-related gene mutations and residual mutations at remission in venetoclax\/azacitidine for AML"],"prefix":"10.1038","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4780-9137","authenticated-orcid":false,"given":"Yoshikazu","family":"Ikoma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1682-7777","authenticated-orcid":false,"given":"Nobuhiko","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Kaneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0179-3335","authenticated-orcid":false,"given":"Hiroyuki","family":"Takamori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomokazu","family":"Seki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0472-6680","authenticated-orcid":false,"given":"Nobuhiro","family":"Hiramoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Kitagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6704-3633","authenticated-orcid":false,"given":"Junya","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8472-6164","authenticated-orcid":false,"given":"Yotaro","family":"Ochi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Chiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Ichii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0945-0513","authenticated-orcid":false,"given":"Kazunori","family":"Imada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4030-4653","authenticated-orcid":false,"given":"Mizuki","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakatsu","family":"Hishizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Miyahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitomo","family":"Maesako","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Oka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8537-2422","authenticated-orcid":false,"given":"Satoshi","family":"Yoshihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinuko","family":"Mitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Kitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4889-7999","authenticated-orcid":false,"given":"Mitsumasa","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuo","family":"Sezaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8959-6271","authenticated-orcid":false,"given":"Tadakazu","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senji","family":"Kasahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7678-4284","authenticated-orcid":false,"given":"Akifumi","family":"Takaori-Kondo","sequence":"additional","affiliation":[],"role":[{"vocabu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Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383:617\u201329.","journal-title":"N Engl J Med"},{"key":"2625_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1182\/blood-2018-08-868752","volume":"133","author":"CD DiNardo","year":"2019","unstructured":"DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133:7\u201317.","journal-title":"Blood"},{"key":"2625_CR3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1182\/blood.2019001239","volume":"135","author":"CD DiNardo","year":"2020","unstructured":"DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. 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NN received honoraria from Nippon Shinyaku Co., Ltd. and AbbVie GK. YK received honoraria from AbbVie GK. NH received honoraria from Nippon Shinyaku Co., Ltd. and AbbVie GK. J. Kanda received honoraria from Nippon Shinyaku Co., Ltd. and AbbVie GK. YO received research funding and honoraria from Nippon Shinyaku Co., Ltd. SC received honoraria from Nippon Shinyaku Co., Ltd. M.Ichii received honoraria from Nippon Shinyaku Co., Ltd. KI received honoraria from Nippon Shinyaku Co., Ltd. and AbbVie GK. SY received honoraria from Nippon Shinyaku Co., Ltd. and AbbVie GK. KM received honoraria from Nippon Shinyaku Co., Ltd. and AbbVie GK. T. Kitano received honoraria from Nippon Shinyaku Co., Ltd. SK received honoraria from AbbVie GK. AT received honoraria from Nippon Shinyaku Co., Ltd. and AbbVie GK. NK received honoraria from AbbVie GK. S.Ogawa received research funding from Nippon Shinyaku Co., Ltd. YN received honoraria from Nippon Shinyaku Co., Ltd. and AbbVie GK.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}