{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:04:20Z","timestamp":1784905460839,"version":"3.55.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100013318","name":"Shanxi Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["YDZJSX2021B009"],"award-info":[{"award-number":["YDZJSX2021B009"]}],"id":[{"id":"10.13039\/501100013318","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017949","name":"Health Commission of Shanxi Province","doi-asserted-by":"publisher","award":["2021XM07"],"award-info":[{"award-number":["2021XM07"]}],"id":[{"id":"10.13039\/100017949","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Oncol"],"DOI":"10.1007\/s12032-025-03054-z","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T04:30:44Z","timestamp":1758256244000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergy Between second-generation FLT3 inhibitors and the ERK1\/2 inhibitor Ulixertinib in FLT3-ITD-mutated acute myeloid leukemia (AML) cells"],"prefix":"10.1007","volume":"42","author":[{"given":"Daniel Muteb","family":"Muyey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuanghui","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanggang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"issue":"23","key":"3054_CR1","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","volume":"374","author":"E Papaemmanuil","year":"2016","unstructured":"Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209\u201321. https:\/\/doi.org\/10.1056\/NEJMoa1516192.","journal-title":"N Engl J Med"},{"issue":"10","key":"3054_CR2","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1002\/ajh.25214","volume":"93","author":"EH Estey","year":"2018","unstructured":"Estey EH. Acute myeloid leukemia: 2019 update on risk-stratification and management. Am J Hematol. 2018;93(10):1267\u201391. https:\/\/doi.org\/10.1002\/ajh.25214.","journal-title":"Am J Hematol"},{"issue":"2","key":"3054_CR3","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1182\/blood-2004-05-1902","volume":"106","author":"M Levis","year":"2005","unstructured":"Levis M, Murphy KM, Pham R, Kim KT, Stine A, Li L, et al. Internal tandem duplications of the FLT3 gene are present in leukemia stem cells. Blood. 2005;106(2):673\u201380. https:\/\/doi.org\/10.1182\/blood-2004-05-1902. (Jul 15;).","journal-title":"Blood"},{"issue":"7397","key":"3054_CR4","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nature11016","volume":"485","author":"CC Smith","year":"2012","unstructured":"Smith CC, Wang Q, Chin CS, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature. 2012;485(7397):260\u20133. https:\/\/doi.org\/10.1038\/nature11016.","journal-title":"Nature"},{"issue":"4","key":"3054_CR5","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1200\/JCO.22.00715","volume":"41","author":"T Grob","year":"2023","unstructured":"Grob T, Sanders MA, Vonk CM, et al. Prognostic value of FLT3-internal tandem duplication residual disease in acute myeloid leukemia. J Clin Oncol. 2023;41(4):756\u201365. https:\/\/doi.org\/10.1200\/JCO.22.00715.","journal-title":"J Clin Oncol"},{"issue":"2","key":"3054_CR6","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1615\/critrevoncog.v17.i2.50","volume":"17","author":"WY Langdon","year":"2012","unstructured":"Langdon WY. FLT3 signaling and the development of inhibitors that target FLT3 kinase activity. Crit Rev Oncog. 2012;17(2):199\u2013209. https:\/\/doi.org\/10.1615\/critrevoncog.v17.i2.50.","journal-title":"Crit Rev Oncog"},{"issue":"23","key":"3054_CR7","doi-asserted-by":"publisher","first-page":"3366","DOI":"10.1182\/blood.2021011583","volume":"139","author":"AE Perl","year":"2022","unstructured":"Perl AE, Larson RA, Podoltsev NA, et al. Follow-up of patients with R\/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022;139(23):3366\u201375. https:\/\/doi.org\/10.1182\/blood.2021011583.","journal-title":"Blood"},{"issue":"1","key":"3054_CR8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41392-021-00870-3","volume":"7","author":"Q Zhang","year":"2022","unstructured":"Zhang Q, Riley-Gillis B, Han L, et al. Activation of RAS\/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia. Signal Transduct Target Ther. 2022;7(1):51. https:\/\/doi.org\/10.1038\/s41392-021-00870-3.","journal-title":"Signal Transduct Target Ther"},{"issue":"S1","key":"3054_CR9","doi-asserted-by":"publisher","first-page":"3338","DOI":"10.1182\/blood-2021-151579","volume":"138","author":"P Sharma","year":"2021","unstructured":"Sharma P, Piya S, Ma H, et al. Erk1\/2 inhibition overcomes resistance in acute myeloid leukemia (AML) and alters mitochondrial dynamics. Blood. 2021;138(S1):3338. https:\/\/doi.org\/10.1182\/blood-2021-151579.","journal-title":"Blood"},{"issue":"5","key":"3054_CR10","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.1007\/s11010-024-05156-0","volume":"480","author":"J Feng","year":"2025","unstructured":"Feng J, Zhang M, Ren H, et al. Human umbilical cord mesenchymal stem cells improve bone marrow hematopoiesis through regulation of bone marrow adipose tissue. Mol Cell Biochem. 2025;480(5):3033\u201349. https:\/\/doi.org\/10.1007\/s11010-024-05156-0.","journal-title":"Mol Cell Biochem"},{"issue":"Pt 20","key":"3054_CR11","doi-asserted-by":"publisher","first-page":"4746","DOI":"10.1242\/jcs.131789","volume":"126","author":"S K\u00f6the","year":"2013","unstructured":"K\u00f6the S, M\u00fcller JP, B\u00f6hmer SA, et al. Features of Ras activation by a mislocalized oncogenic tyrosine kinase: FLT3 ITD signals through K-Ras at the plasma membrane of acute myeloid leukemia cells. J Cell Sci. 2013;126(Pt 20):4746\u201355. https:\/\/doi.org\/10.1242\/jcs.131789.","journal-title":"J Cell Sci"},{"issue":"1","key":"3054_CR12","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1080\/21541248.2017.1339765","volume":"11","author":"EJ Pomeroy","year":"2020","unstructured":"Pomeroy EJ, Eckfeldt CE. Targeting Ras signaling in AML: RALB is a small GTPase with big potential. Small GTPases. 2020;11(1):39\u201344. https:\/\/doi.org\/10.1080\/21541248.2017.1339765.","journal-title":"Small GTPases."},{"issue":"6","key":"3054_CR13","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1182\/blood.v97.6.1823","volume":"97","author":"MA Morgan","year":"2001","unstructured":"Morgan MA, Dolp O, Reuter CW. Cell-cycle-dependent activation of mitogen-activated protein kinase kinase (MEK-1\/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling. Blood. 2001;97(6):1823\u201334. https:\/\/doi.org\/10.1182\/blood.v97.6.1823.","journal-title":"Blood"},{"issue":"7","key":"3054_CR14","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1182\/bloodadvances.2021006489","volume":"6","author":"CC Smith","year":"2022","unstructured":"Smith CC, Levis MJ, Perl AE, et al. Molecular profile of FLT3-mutated relapsed\/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib. Blood Adv. 2022;6(7):2144\u201355. https:\/\/doi.org\/10.1182\/bloodadvances.2021006489.","journal-title":"Blood Adv"},{"issue":"16","key":"3054_CR15","doi-asserted-by":"publisher","first-page":"4402","DOI":"10.1158\/0008-5472.CAN-16-1627","volume":"77","author":"P Hou","year":"2017","unstructured":"Hou P, Wu C, Wang Y, et al. A genome-wide CRISPR screen identifies genes critical for resistance to FLT3 inhibitor AC220. Cancer Res. 2017;77(16):4402\u201313. https:\/\/doi.org\/10.1158\/0008-5472.CAN-16-1627.","journal-title":"Cancer Res"},{"issue":"6","key":"3054_CR16","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/s41419-018-0691-x","volume":"9","author":"A Yallowitz","year":"2018","unstructured":"Yallowitz A, Ghaleb A, Garcia L, et al. Heat shock factor 1 confers resistance to lapatinib in ERBB2-positive breast cancer cells. Cell Death Dis. 2018;9(6):621. https:\/\/doi.org\/10.1038\/s41419-018-0691-x.","journal-title":"Cell Death Dis"},{"issue":"3","key":"3054_CR17","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.3892\/etm.2020.8454","volume":"19","author":"YJ Guo","year":"2020","unstructured":"Guo YJ, Pan WW, Liu SB, et al. ERK\/MAPK signalling pathway and tumorigenesis. Exp Ther Med. 2020;19(3):1997\u20132007. https:\/\/doi.org\/10.3892\/etm.2020.8454.","journal-title":"Exp Ther Med"},{"issue":"1","key":"3054_CR18","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1517\/14728222.2011.645805","volume":"16","author":"L Santarpia","year":"2012","unstructured":"Santarpia L, Lippman SM, El-Naggar AK. Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012;16(1):103\u201319. https:\/\/doi.org\/10.1517\/14728222.2011.645805.","journal-title":"Expert Opin Ther Targets"},{"issue":"4","key":"3054_CR19","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1007\/s40135-021-00277-x","volume":"9","author":"ST Hsu","year":"2021","unstructured":"Hsu ST, Ponugoti A, Deaner JD, et al. Update on retinal drug toxicities. Curr Ophthalmol Rep. 2021;9(4):168\u201377. https:\/\/doi.org\/10.1007\/s40135-021-00277-x.","journal-title":"Curr Ophthalmol Rep"},{"key":"3054_CR20","doi-asserted-by":"publisher","DOI":"10.2174\/0109298673311108240926062214","author":"F Ge","year":"2024","unstructured":"Ge F, Wang Y, Chen P, et al. FOXN3-AS1: a candidate prognostic marker and epigenetic target with immunotherapeutic implications in acute myeloid leukemia. Curr Med Chem. 2024. https:\/\/doi.org\/10.2174\/0109298673311108240926062214.","journal-title":"Curr Med Chem"},{"issue":"4","key":"3054_CR21","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2024.12449","volume":"27","author":"Y Su","year":"2024","unstructured":"Su Y, Wu M, Zhou B, et al. Paclitaxel mediates the PI3K\/AKT\/mTOR pathway to reduce proliferation of FLT3-ITD(+) AML cells and promote apoptosis. Exp Ther Med. 2024;27(4):161. https:\/\/doi.org\/10.3892\/etm.2024.12449.","journal-title":"Exp Ther Med"},{"issue":"3","key":"3054_CR22","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s40265-019-1062-3","volume":"79","author":"S Dhillon","year":"2019","unstructured":"Dhillon S. Gilteritinib: first global approval. Drugs. 2019;79(3):331\u20139. https:\/\/doi.org\/10.1007\/s40265-019-1062-3.","journal-title":"Drugs"},{"issue":"1","key":"3054_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07337-1","volume":"16","author":"Y Wang","year":"2025","unstructured":"Wang Y, Kroll TG, Hao L, et al. Orphan nuclear receptor NR2E3 is a new molecular vulnerability in solid tumors by activating p53. Cell Death Dis. 2025;16(1):15. https:\/\/doi.org\/10.1038\/s41419-025-07337-1.","journal-title":"Cell Death Dis"},{"issue":"5","key":"3054_CR24","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.yexcr.2012.01.001","volume":"318","author":"M Karam","year":"2012","unstructured":"Karam M, Legay C, Auclair C, et al. Protein kinase D1 stimulates proliferation and enhances tumorigenesis of MCF-7 human breast cancer cells through a MEK\/ERK-dependent signaling pathway. Exp Cell Res. 2012;318(5):558\u201369. https:\/\/doi.org\/10.1016\/j.yexcr.2012.01.001.","journal-title":"Exp Cell Res"},{"issue":"9","key":"3054_CR25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046038","volume":"7","author":"N Qiu","year":"2012","unstructured":"Qiu N, Xiao Z, Cao L, et al. Conditional mesenchymal disruption of pkd1 results in osteopenia and polycystic kidney disease. PLoS ONE. 2012;7(9):e46038. https:\/\/doi.org\/10.1371\/journal.pone.0046038.","journal-title":"PLoS ONE"},{"issue":"12","key":"3054_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11123194","volume":"11","author":"YQ Guo","year":"2023","unstructured":"Guo YQ, Gan MF, Bao JQ, et al. KDF1 promoted proliferation, migration and invasion of lung adenocarcinoma cells through activating STAT3 and AKT pathway. Biomedicines. 2023;11(12):3194. https:\/\/doi.org\/10.3390\/biomedicines11123194.","journal-title":"Biomedicines"},{"issue":"3\u20134","key":"3054_CR27","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1159\/000453136","volume":"40","author":"L Zhang","year":"2016","unstructured":"Zhang L, Jia G, Shi B, et al. PRSS8 is downregulated and suppresses tumour growth and metastases in hepatocellular carcinoma. Cell Physiol Biochem. 2016;40(3\u20134):757\u201369. https:\/\/doi.org\/10.1159\/000453136.","journal-title":"Cell Physiol Biochem"},{"issue":"5","key":"3054_CR28","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1139\/bcb-2019-0446","volume":"98","author":"L Wu","year":"2020","unstructured":"Wu L, Gong Y, Yan T, et al. LINP1 promotes the progression of cervical cancer by scaffolding EZH2, LSD1, and DNMT1 to inhibit the expression of KLF2 and PRSS8. Biochem Cell Biol. 2020;98(5):591\u20139. https:\/\/doi.org\/10.1139\/bcb-2019-0446.","journal-title":"Biochem Cell Biol"},{"issue":"4","key":"3054_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107152","volume":"300","author":"X Zhao","year":"2024","unstructured":"Zhao X, Lv S, Li N, et al. YTHDF2 protein stabilization by the deubiquitinase OTUB1 promotes prostate cancer cell proliferation via PRSS8 mRNA degradation. J Biol Chem. 2024;300(4):107152. https:\/\/doi.org\/10.1016\/j.jbc.2024.107152.","journal-title":"J Biol Chem"},{"issue":"5","key":"3054_CR30","doi-asserted-by":"publisher","first-page":"781","DOI":"10.3727\/096504016X14772417575982","volume":"25","author":"C Ma","year":"2017","unstructured":"Ma C, Ma W, Zhou N, et al. Protease serine S1 family member 8 (PRSS8) inhibits tumor growth in vitro and in vivo in human non-small cell lung cancer. Oncol Res. 2017;25(5):781\u20137. https:\/\/doi.org\/10.3727\/096504016X14772417575982.","journal-title":"Oncol Res"},{"key":"3054_CR31","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/bs.ircmb.2021.05.003","volume":"362","author":"M Bonora","year":"2021","unstructured":"Bonora M, Kahsay A, Pinton P. Mitochondrial calcium homeostasis in hematopoietic stem cell: Molecular regulation of quiescence, function, and differentiation. Int Rev Cell Mol Biol. 2021;362:111\u201340. https:\/\/doi.org\/10.1016\/bs.ircmb.2021.05.003.","journal-title":"Int Rev Cell Mol Biol"},{"issue":"20","key":"3054_CR32","doi-asserted-by":"publisher","first-page":"3354","DOI":"10.1158\/0008-5472.CAN-23-3560","volume":"84","author":"C Schneider","year":"2024","unstructured":"Schneider C, Spaink H, Alexe G, et al. Targeting the sodium-potassium pump as a therapeutic strategy in acute myeloid leukemia. Cancer Res. 2024;84(20):3354\u201370. https:\/\/doi.org\/10.1158\/0008-5472.CAN-23-3560.","journal-title":"Cancer Res"}],"container-title":["Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-03054-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12032-025-03054-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-03054-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T10:23:51Z","timestamp":1762424631000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12032-025-03054-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,19]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["3054"],"URL":"https:\/\/doi.org\/10.1007\/s12032-025-03054-z","relation":{},"ISSN":["1559-131X"],"issn-type":[{"value":"1559-131X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,19]]},"assertion":[{"value":"3 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"479"}}