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Although the associations of acquired genetic alterations with patients\u2019 sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols. A validation cohort comprised 465 women and 489 men treated on frontline protocols of the German AML Cooperative Group. Compared with men, women more often had normal karyotype,\n                    <jats:italic>FLT3<\/jats:italic>\n                    -ITD,\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    ,\n                    <jats:italic>NPM1<\/jats:italic>\n                    and\n                    <jats:italic>WT1<\/jats:italic>\n                    mutations and less often complex karyotype,\n                    <jats:italic>ASXL1<\/jats:italic>\n                    ,\n                    <jats:italic>SRSF2<\/jats:italic>\n                    ,\n                    <jats:italic>U2AF1<\/jats:italic>\n                    ,\n                    <jats:italic>RUNX1<\/jats:italic>\n                    , or\n                    <jats:italic>KIT<\/jats:italic>\n                    mutations. More women were in the 2022 European LeukemiaNet intermediate-risk group and more men in adverse-risk group. We found sex differences in co-occurring mutation patterns and prognostic impact of select genetic alterations. The mutation-associated splicing events and gene-expression profiles also differed between sexes. In patients aged &lt;60 years,\n                    <jats:italic>SF3B1<\/jats:italic>\n                    mutations were male-specific adverse outcome prognosticators. We conclude that sex differences in AML-associated genetic alterations and mutation-specific differential splicing events highlight the importance of patients\u2019 sex in analyses of AML biology and prognostication.\n                  <\/jats:p>","DOI":"10.1038\/s41375-023-02068-8","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T04:02:35Z","timestamp":1701144155000},"page":"45-57","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, 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JSB is a consultant\/advisory board member for AbbVie, AstraZeneca, INNATE, KITE. BLP received honoraria from Jazz Pharmaceuticals, Novartis, and Pfizer. JEK has received honoraria from Gilead, Magellan, and Novartis; consulting fees from Gilead, Magellan, Novartis, Pharmacyclics, and Seattle Genetics; institutional research funding from Boehringer Ingelheim, Cantex, Erytech, and Millennium; and travel support from Gilead, Novartis, and Seattle Genetics. JCB has a consultancy\/advisory role with Syndax, Novartis, Vincera; research funding from Pharmacyclics LLC, an AbbVie Company, Genentech, Janssen, Acerta; ownership for Vincera. A-KE has a current employment of her spouse at Karyopharm Therapeutics. The other authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}