{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:06:18Z","timestamp":1753862778381,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370176","82470117","81900116"],"award-info":[{"award-number":["82370176","82470117","81900116"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hyperleukocytic acute myeloid leukemia (HL\u2010AML) is associated with early complications and high mortality rates, highlighting the urgent need for more effective therapeutic strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study conducted label\u2010free proteomic analysis on serum from HL\u2010AML and non\u2010HL AML (NHL\u2010AML) patients, integrating the data with the OHSU transcriptomic database. Flow cytometry was used to evaluate the in\u00a0vitro impact of bortezomib. The in\u00a0vivo effectiveness of bortezomib was assessed using the patient\u2010derived xenograft (PDX) model of HL\u2010AML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Through integrated analysis of serum proteomics and transcriptomics, we observed an abnormal enrichment of the NF\u2010kappa B pathway in HL\u2010AML, suggesting its potential as a novel therapeutic target. Given that bortezomib is an inhibitor of the NF\u2010kappa B pathway, HL\u2010AML bone marrow cells were treated with varying concentrations of bortezomib (0, 5, 10, and 20\u2009nM) in\u00a0vitro. The results indicated a significant cytotoxic effect of bortezomib on HL\u2010AML cells, accompanied by increased apoptosis rates and decreased proliferation. Co\u2010administration of bortezomib with the frontline clinical chemotherapeutic regimen of daunorubicin and cytarabine (DA regimen) significantly extended mouse survival. Bone marrow immunophenotyping showed reductions in CD45<jats:sup>+<\/jats:sup> and CD33<jats:sup>+<\/jats:sup> cell populations, indicating disease amelioration. Immunohistochemical analysis further confirmed the inhibitory effect on the NF\u2010kappa B pathway, as evidenced by reduced levels of P\u2010IKB\u03b1 and P\u2010p65 proteins, validating the proposed therapeutic mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that combination therapy involving bortezomib and the DA regimen may represent a promising strategy for HL\u2010AML.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70438","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T12:40:35Z","timestamp":1732538435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omic Analysis Reveals the Impact of Bortezomib in Hyperleukocytic Acute Myeloid Leukemia"],"prefix":"10.1002","volume":"13","author":[{"given":"Jinxian","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2350-866X","authenticated-orcid":false,"given":"Bei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanyue","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruihang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guopeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiqin","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-0382","authenticated-orcid":false,"given":"Fuling","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hematology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Research Center for Lifespan Health Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_11_2_1","DOI":"10.1056\/NEJMra1406184"},{"doi-asserted-by":"publisher","key":"e_1_2_11_3_1","DOI":"10.1016\/S0140-6736(06)69780-8"},{"doi-asserted-by":"publisher","key":"e_1_2_11_4_1","DOI":"10.3324\/haematol.2017.184267"},{"doi-asserted-by":"publisher","key":"e_1_2_11_5_1","DOI":"10.1182\/blood-2014-10-551507"},{"doi-asserted-by":"publisher","key":"e_1_2_11_6_1","DOI":"10.1002\/hon.2292"},{"doi-asserted-by":"publisher","key":"e_1_2_11_7_1","DOI":"10.1080\/17474086.2020.1751609"},{"doi-asserted-by":"publisher","key":"e_1_2_11_8_1","DOI":"10.1016\/j.blre.2012.01.003"},{"doi-asserted-by":"publisher","key":"e_1_2_11_9_1","DOI":"10.3109\/10428190009053534"},{"doi-asserted-by":"publisher","key":"e_1_2_11_10_1","DOI":"10.3390\/cancers15123072"},{"doi-asserted-by":"publisher","key":"e_1_2_11_11_1","DOI":"10.1177\/20406207221132346"},{"key":"e_1_2_11_12_1","first-page":"1160","article-title":"Proteomics for Cancer Biomarker Discovery","volume":"48","author":"Srinivas P. 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