{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T21:02:59Z","timestamp":1784408579656,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170205"],"award-info":[{"award-number":["82170205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300240"],"award-info":[{"award-number":["82300240"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,7]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>KMT2A<\/jats:italic>(11q23)\u2010rearranged acute myeloid leukemia (KMT2A<\/jats:italic>\u2010r AML) represents a clinically aggressive subtype with heterogeneous outcomes. Current evidence remains inconclusive regarding the prognostic relevance of fusion partners in 11q23\/KMT2A<\/jats:italic>\u2010rearranged AML. The comprehensive mutational landscape and prognostic implications of co\u2010occurring driver mutations remain poorly characterized.<\/jats:p><\/jats:sec>Methods<\/jats:title>A comprehensive clinicogenomic analysis of 159 de novo KMT2A<\/jats:italic>\u2010r AML patients was conducted to assess the correlation between molecular profiles and clinical outcomes.<\/jats:p><\/jats:sec>Results<\/jats:title>Notably, the KMT2A::MLLT4<\/jats:italic> subgroup exhibited significantly higher KRAS<\/jats:italic> mutation frequencies compared to other rearrangement groups (p<\/jats:italic>\u00a0<\u00a0.05). Survival analysis revealed that the KMT2A::MLLT4<\/jats:italic> cohort demonstrated trends toward inferior overall survival (OS) and increased cumulative incidence of relapse (CIR) relative to other rearrangement subgroups. Stratified by mutational status, patients with KRAS<\/jats:italic> mutations exhibited significantly inferior 2\u2010year OS rates (24.6% vs. 50.5%; p<\/jats:italic>\u00a0=\u00a0.001) and higher 2\u2010year CIR (56.3% vs. 34.6%; p<\/jats:italic>\u00a0=\u00a0.018) compared to KRAS<\/jats:italic> wild\u2010type counterparts. This adverse prognostic association remained in the transplanted cohort (OS: 32.3% vs. 73.5%; p<\/jats:italic>\u00a0<\u00a0.001; CIR: 73.6% vs. 23.0%; p<\/jats:italic>\u00a0<\u00a0.001). In contrast, mutations in NRAS<\/jats:italic>, FLT3<\/jats:italic> did not demonstrate statistically significant associations with OS or CIR in either the overall cohort or transplant subgroup. Multivariable Cox regression confirmed KRAS<\/jats:italic> mutation as an independent adverse prognostic factor for both 2\u2010year OS (hazard ratio [HR],\u00a00.51; 95% CI, 0.31\u20130.84; p<\/jats:italic>\u00a0=\u00a0.008) and CIR (HR,\u00a01.80; 95% CI, 1.04\u20133.12; p<\/jats:italic>\u00a0=\u00a0.037) in the overall cohort. This association persisted in the transplanted patients subgroup (OS: HR,\u00a00.18; 95% CI, 0.06\u20130.52; p<\/jats:italic>\u00a0=\u00a0.001; CIR: HR,\u00a03.89; 95% CI, 1.05\u201314.37; p<\/jats:italic>\u00a0=\u00a0.042).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>These results demonstrate the independent prognostic value of KRAS<\/jats:italic> mutations across treatment modalities, including both conventional chemotherapy and hematopoietic stem cell transplantation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35941","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T10:03:22Z","timestamp":1751191402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["KRAS mutation status critically determines the clinical outcome of patients with KMT2A\u2010rearranged acute myeloid leukemia"],"prefix":"10.1002","volume":"131","author":[{"given":"Yibo","family":"Wu","sequence":"first","affiliation":[{"name":"Bone Marrow Transplantation Center of the First Affiliated Hospital & Liangzhu Laboratory Zhejiang University School of Medicine Hangzhou China"},{"name":"Institute of Hematology Zhejiang University Hangzhou China"},{"name":"Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center of the First Affiliated Hospital & Liangzhu Laboratory Zhejiang University School of Medicine Hangzhou China"},{"name":"Institute of Hematology Zhejiang University Hangzhou China"},{"name":"Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy Hangzhou China"},{"name":"Department of Hematology Zhejiang Cancer Hospital Hangzhou Institute of Medicine 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