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This real-life study compared mutation profiles and their impact on outcomes in 80 AYA, 97 adult, and 16 pediatric CML-CP patients, alongside 81\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    -positive acute lymphoblastic leukemia (Ph+\u00a0ALL) patients. CRG mutations were more frequent in AYAs (25.0%) than in adults (19.6%) or children (12.5%). AYAs with Ph+ ALL exhibited higher mutational frequencies (53.3%) compared to children (26.7%) and adults (38.9%). At diagnosis, mutations in\n                    <jats:italic>ASXL1<\/jats:italic>\n                    ,\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    , and\n                    <jats:italic>TET2<\/jats:italic>\n                    dominated in CML-CP and\n                    <jats:italic>RUNX1<\/jats:italic>\n                    ,\n                    <jats:italic>IKZF1<\/jats:italic>\n                    , and\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    in Ph+ ALL.\n                    <jats:italic>ASXL1<\/jats:italic>\n                    mutations correlated with reduced progression-free survival (PFS) in AYAs and adults. Unlike adults, AYAs showed no increase in\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    kinase domain mutations during TKI therapy. Nilotinib improved PFS in AYAs with\n                    <jats:italic>ASXL1<\/jats:italic>\n                    mutations, highlighting the efficacy of higher-generation TKIs.\n                    <jats:italic>ASXL1<\/jats:italic>\n                    mutations also impaired erythropoiesis, warranting further validation. Despite a higher mutational burden, AYAs did not exhibit worse prognoses than adults. Lower mutation rates at follow-up suggest potential impact of nilotinib. Mutation profiling and optimized TKI use are crucial to mitigate progression risks in CRG-mutated patients.\n                  <\/jats:p>","DOI":"10.1038\/s41375-025-02609-3","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T03:45:44Z","timestamp":1745811944000},"page":"1670-1677","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Somatic mutations and outcomes in chronic myeloid leukemia adolescent and young adults compared to children, adults, and BCR::ABL1-positive acute lymphoblastic leukemia"],"prefix":"10.1038","volume":"39","author":[{"given":"Jitka","family":"Krizkova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaclava","family":"Polivkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Laznicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"Curik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Benesova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2611-5848","authenticated-orcid":false,"given":"Pavla","family":"Suchankova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5413-0766","authenticated-orcid":false,"given":"Tomas","family":"Smazik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Vysinova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Mikulenkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5020-7040","authenticated-orcid":false,"given":"Hana","family":"Klamova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marketa Stastna","family":"Markova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Srbova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0887-3709","authenticated-orcid":false,"given":"Jan","family":"Zuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1639-7124","authenticated-orcid":false,"given":"Marketa","family":"Zaliova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-8608","authenticated-orcid":false,"given":"Jan","family":"Trka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0021-3247","authenticated-orcid":false,"given":"Cyril","family":"Salek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7398-5555","authenticated-orcid":false,"given":"Katerina Machova","family":"Polakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"2609_CR1","first-page":"389","volume":"28","author":"JE Cortes","year":"2010","unstructured":"Cortes JE, Jones D, O\u2019Brien S, Jabbour E, Ravandi F, Koller C, et al. 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The remaining authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The project was approved by the local Ethics Review Committee (EK 1\/AZV \u010cR\/06\/2020).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients, as well as the parents of paediatric patients, provided written informed consent for the use of their samples and clinical data in the research project, in accordance with the Declaration of Helsinki and institutional guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}