{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T14:18:46Z","timestamp":1768573126850,"version":"3.49.0"},"posted":{"date-parts":[[2025,11,6]]},"group-title":"Hematology","reference-count":15,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Nucleophosmin-1 (\n                  <jats:italic>NPM1<\/jats:italic>\n                  ) mutations define a major molecular subtype of acute myeloid leukemia (AML) and is generally associated with favorable prognosis. However, the impact of myelodysplasia-associated mutations (MDSm+) on patient outcomes within this subgroup remains uncertain. We retrospectively analyzed 271\n                  <jats:italic>NPM1<\/jats:italic>\n                  -mutated AML patients from three independent cohorts (SWOG, Fred Hutch, and Beat AML) to assess the prognostic significance of MDSm+ and its interaction with age. MDSm+ occurred in 17% of cases, most commonly involving\n                  <jats:italic>SRSF2<\/jats:italic>\n                  and\n                  <jats:italic>SF3B1<\/jats:italic>\n                  . Although MDSm+ was associated with inferior overall survival compared to MDSm-in ELN2022 favorable-risk patients (HR 2.0,\n                  <jats:italic>p<\/jats:italic>\n                  =0.008), this effect was largely driven by worse outcomes in older patients (\n                  <jats:sub>\u2265<\/jats:sub>\n                  65 years) as older ELN22 favorable-risk patients had poor OS regardless of presence of MDSm+ compared to younger patients. After stratification of patients by age, there was not a significant difference between MDSm+ and MDSm-in either younger patients (HR 0.99, p=0.98) or older patients (HR 1.42,\n                  <jats:italic>p<\/jats:italic>\n                  =0.33). These findings indicate that MDSm+ in\n                  <jats:italic>NPM1<\/jats:italic>\n                  + AML is not independently associated with adverse risk after adjusting for age and highlight the need for age-adjusted AML risk models.\n                <\/jats:p>","DOI":"10.1101\/2025.11.03.25339099","type":"posted-content","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T21:15:22Z","timestamp":1762463722000},"source":"Crossref","is-referenced-by-count":0,"title":["Prognostic impact of age and MDS-associated mutations in\n                  <i>NPM1<\/i>\n                  -mutated AML"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9118-6204","authenticated-orcid":false,"given":"Vivian M.","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8176-6371","authenticated-orcid":false,"given":"Megan","family":"Othus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3957-4039","authenticated-orcid":false,"given":"Jasmine","family":"Naru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3702-7923","authenticated-orcid":false,"given":"Rhonda E.","family":"Ries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9060-358X","authenticated-orcid":false,"given":"Era L.","family":"Pogosova-Agadjanyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1839-5069","authenticated-orcid":false,"given":"Frederick R.","family":"Appelbaum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-7301","authenticated-orcid":false,"given":"Thomas R.","family":"Chauncey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8836-0374","authenticated-orcid":false,"given":"Eliana","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1093-2189","authenticated-orcid":false,"given":"Harry P.","family":"Erba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John 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C.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7514-7360","authenticated-orcid":false,"given":"Anna","family":"Moseley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary-Elizabeth","family":"Percival","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8836-1246","authenticated-orcid":false,"given":"Guangrong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerald 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Comprehensive Age-Stratified Impact of. Cancers (Basel). 2025;17(6).","DOI":"10.3390\/cancers17061020"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.11.03.25339099","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:50:25Z","timestamp":1768510225000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.11.03.25339099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":15,"URL":"https:\/\/doi.org\/10.1101\/2025.11.03.25339099","relation":{},"subject":[],"published":{"date-parts":[[2025,11,6]]},"subtype":"preprint"}}