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We investigated NK\u2010AML in a large paediatric AML cohort from four trials of the Nordic Society for Paediatric Haematology and Oncology\u2010Dutch Belgian Hongkong (NOPHO\u2010DBH) group. Among 1476 AML patients, we identified 316 NK\u2010AML patients (21%). NK\u2010AML was characterized by high frequencies of <jats:italic>FLT3<\/jats:italic> internal tandem duplications (ITD, 33%), mutated <jats:italic>NPM1<\/jats:italic> (28%), <jats:italic>WT1<\/jats:italic> (25%) and <jats:italic>CEBPA<\/jats:italic> (21%). Five\u2010year event\u2010free survival (EFS) and overall survival (OS) in NK\u2010AML were 52% (95% confidence interval [CI]: 46\u201358) and 70% (CI: 65\u201375) respectively. Restricted to <jats:italic>NPM1<\/jats:italic><jats:sup>wt<\/jats:sup> cases only (<jats:italic>n<\/jats:italic>\u2009=\u2009959), NK\u2010AML was associated with unfavourable outcome (relative risk [RR] of EFS\u2009=\u20090.80, <jats:italic>p<\/jats:italic>\u2009=\u20090.014; RR of OS\u2009=\u20090.87, <jats:italic>p<\/jats:italic>\u2009=\u20090.022). NK\u2010AML with mutated <jats:italic>NPM1<\/jats:italic> had excellent EFS (79%, CI: 66\u201388) and OS (97%, CI: 88\u201399), which was not influenced by concomitant <jats:italic>FLT3<\/jats:italic>\u2010ITD. In multivariable analysis, mutated <jats:italic>NPM1<\/jats:italic> in NK\u2010AML was associated with favourable EFS (hazard ratio [HR]: 0.24, CI: 0.13\u20130.43, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and OS (HR: 0.10, CI: 0.03\u20130.35, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). <jats:italic>FLT3<\/jats:italic>\u2010ITD was associated with inferior EFS (HR: 1.56, CI: 1.03\u20132.35, <jats:italic>p<\/jats:italic>\u2009=\u20090.035) and OS (HR: 1.91, CI: 1.11\u20133.31, <jats:italic>p<\/jats:italic>\u2009=\u20090.02). We conclude that prognosis in paediatric NK\u2010AML is independently affected by <jats:italic>NPM1<\/jats:italic> and <jats:italic>FLT3<\/jats:italic>\u2010ITD status. Further molecular characterization of NK\u2010AML is needed, especially for <jats:italic>NPM1<\/jats:italic><jats:sup>wt<\/jats:sup> NK\u2010AML.<\/jats:p>","DOI":"10.1111\/bjh.70094","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T05:44:48Z","timestamp":1755582288000},"page":"1454-1463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characteristics and prognosis of paediatric normal karyotype acute myeloid leukaemia: A <scp>NOPHO<\/scp>\u2010<scp>DBH AML<\/scp> study"],"prefix":"10.1111","volume":"207","author":[{"given":"Morten Krogh","family":"Herlin","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eigil","family":"Kjeldsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Haematology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Abrahamsson","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Institution for Clinical Sciences, Queen Silvia Children's Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nira","family":"Arad\u2010Cohen","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haemato\u2010Oncology Rambam Medical Centre  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Cheuk","sequence":"additional","affiliation":[{"name":"Hong Kong Paediatric Haematology and Oncology Study Group (HKPHOSG), Department of Paediatrics and Adolescent Medicine Hong Kong Children's Hospital  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"De Moerloose","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology\u2010Oncology Ghent University Hospital  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsi","family":"Jahnukainen","sequence":"additional","affiliation":[{"name":"New Children's Hospital, Paediatric Research Centre University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3lafur G\u00edsli","family":"J\u00f3nsson","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Landspitalinn  Reykjavik Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertjan J. L.","family":"Kaspers","sequence":"additional","affiliation":[{"name":"Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Princess Maxima Centre for Paediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanna","family":"Kovalova","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology\/Haematology Children's Clinical University Hospital  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Maria Fernandez","family":"Navarro","sequence":"additional","affiliation":[{"name":"Hospital Universitario y Polit\u00e9cnico La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika","family":"Noren\u2010Nystr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Ume\u00e5 University Hospital  Ume\u00e5 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