{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:02:10Z","timestamp":1790488930569,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":39,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Acute myeloid leukemia (AML) is a heterogeneous disease, and its heterogeneity is associated with treatment response. Despite the demonstrated success of venetoclax (VEN)\u2010based therapy for AML, the effect of FLT3 mutations on the efficacy of the therapy is poorly understood. We aimed to compare the efficacy of VEN\u2010based therapy between FLT3\u2010mutated (FLT3<jats:sup>mut<\/jats:sup>) and FLT3 wild\u2010type (FLT3<jats:sup>wt<\/jats:sup>) patients and identify the predictors of efficacy in FLT3<jats:sup>mut<\/jats:sup> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 266 AML patients (127 newly diagnosed [ND] and 139 refractory\/relapsed [R\/R]) receiving VEN\u2010based regimens were enrolled in this study. A retrospective analysis was performed, and the treatment responses and overall survival (OS) of FLT3<jats:sup>mut<\/jats:sup> and FLT3<jats:sup>wt<\/jats:sup> patients were compared. Logistic regression and Cox proportional hazards model were applied to examine the clinical and genetic predictors of outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>With a median of two cycles of VEN\u2010based therapy, for the ND AML cohort, the FLT3<jats:sup>mut<\/jats:sup> group had a comparable composite complete remission (CRc) rate with the FLT3<jats:sup>wt<\/jats:sup> group (79.3% vs. 61.2%, <jats:italic>p<\/jats:italic>\u2009=\u20090.072). For the R\/R AML cohort, the FLT3<jats:sup>mut<\/jats:sup> group exhibited a lower CRc rate than the FLT3<jats:sup>wt<\/jats:sup> group. With a median follow\u2010up of 8.6\u2009months (95% confidence interval [CI], 8.0\u201310), the median OS observed in the FLT3<jats:sup>mut<\/jats:sup> and FLT3<jats:sup>wt<\/jats:sup> groups for both cohorts were close (14.0 vs. 19.9\u2009months, <jats:italic>p<\/jats:italic>\u2009=\u20090.356; 10.0 vs. 11.9\u2009months, <jats:italic>p<\/jats:italic>\u2009=\u20090.680). For the ND AML cohort, in FLT3<jats:sup>mut<\/jats:sup> patients, MRD\u2010positive and RNA\u2010splicing mutation predicted inferior survival (hazard ratio [HR], 10.3; 95% CI: 2.0\u201353.8; <jats:italic>p<\/jats:italic>\u2009=\u20090.006; HR 11.3; 95% CI: 1.2\u2013109.3; <jats:italic>p<\/jats:italic>\u2009=\u20090.036, respectively). For the R\/R AML cohort, in FLT3<jats:sup>mut<\/jats:sup> patients, adverse ELN risk was associated with an inferior response (odds ratio [OR], 0.2; 95% CI: 0.1\u20130.8; <jats:italic>p<\/jats:italic>\u2009=\u20090.025), whereas NPM1 co\u2010mutation was associated with a superior response (57.1%; OR, 6.7; 95% CI: 1.5\u201330.1; <jats:italic>p<\/jats:italic>\u2009=\u20090.014). CR\/CRi predicted a better survival (HR 0.2; 95% CI: 0.1\u20130.8; <jats:italic>p<\/jats:italic>\u2009=\u20090.029), while DNMT3A mutation predicted an inferior survival (HR, 4.6; 95% CI: 1.4\u201314.9; <jats:italic>p<\/jats:italic>\u2009=\u20090.011).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FLT3 mutations may influence response to VEN\u2010based therapy in R\/R AML patients but not in ND AML patients. Furthermore, clinical and genetic characteristics could predict outcomes of FLT3<jats:sup>mut<\/jats:sup> patients receiving VEN\u2010based therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6885","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T14:53:55Z","timestamp":1707490435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical and genetic characteristics predict outcomes of acute myeloid leukemia patients with <scp>FLT3<\/scp> mutations receiving venetoclax\u2010based therapy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7923-8972","authenticated-orcid":false,"given":"Guangyang","family":"Weng","sequence":"first","affiliation":[{"name":"Department of Hematology and Shenzhen Bone Marrow Transplantation Public Service Platform The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingya","family":"Huang","sequence":"additional","affiliation":[{"name":"Shenzhen Blood Center  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"An","sequence":"additional","affiliation":[{"name":"Department of Hematology and Shenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Institute of Hematology, Shenzhen Second People's Hospital The First Affiliated Hospital of Shenzhen University, Shenzhen University Health Sciences Center  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology Nanfang Hospital, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guopan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Hematology Nanfang Hospital, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hematology, Shenzhen Hospital Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hematology the Seventh Affiliated Hospital of Sun Yat\u2010Sen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinquan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Hematology The First People's Hospital of Chenzhou  Chenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Hematology Sun Yat\u2010Sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongshan City People's Hospital  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongshan City People's Hospital  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-0249","authenticated-orcid":false,"given":"Hua","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Hematology Nanfang Hospital, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4015-3952","authenticated-orcid":false,"given":"Qifa","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology Nanfang Hospital, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Hematology and Shenzhen Bone Marrow Transplantation Public Service Platform The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-08-868752"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2012971"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003988"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016867"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003734"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25000"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-020-03911-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03736"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13581"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00495-3"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00715"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0357-9"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25929"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3405"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01600"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301689"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516192"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-643544"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-733196"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0686-3"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-022-00677-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0694-3"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.630429"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-117179"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.188094"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3467"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221810040"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01222-4"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008211"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-01017-7"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30455-1"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-578070"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112304"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1005143"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.6885","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T06:36:14Z","timestamp":1709534174000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.6885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/cam4.6885"],"URL":"https:\/\/doi.org\/10.1002\/cam4.6885","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2023-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e6885"}}