{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:01:11Z","timestamp":1784779271867,"version":"3.55.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Central Government Guidance Funds for Local Scientific and Technological Development, China","award":["236Z7736G"],"award-info":[{"award-number":["236Z7736G"]}]},{"name":"Hebei Provincial Health Commission Government-Funded Clinical Medicine Talent Program","award":["ZF2024048"],"award-info":[{"award-number":["ZF2024048"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s00210-026-05387-6","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:37:57Z","timestamp":1777873077000},"page":"15839-15852","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined inhibition of DOT1L and BCL-2 induces synergistic anti-leukemic effects in MLL-rearranged acute myeloid leukemia via suppression of the PI3K\/AKT pathway"],"prefix":"10.1007","volume":"399","author":[{"given":"Yabei","family":"Zuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daitianchang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"5387_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11030461","author":"HA Alkhatabi","year":"2022","unstructured":"Alkhatabi HA, Zohny SF, Shait Mohammed MR, Choudhry H, Rehan M, Ahmad A, Ahmed F, Khan MI (2022) Venetoclax-resistant MV4-11 leukemic cells activate PI3K\/AKT pathway for metabolic reprogramming and redox adaptation for survival. Antioxidants (Basel). https:\/\/doi.org\/10.3390\/antiox11030461","journal-title":"Antioxidants (Basel)"},{"issue":"4","key":"5387_CR2","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/ng.3230","volume":"47","author":"AK Andersson","year":"2015","unstructured":"Andersson AK, Ma J, Wang J, Chen X, Gedman AL, Dang J, Nakitandwe J, Holmfeldt L, Parker M, Easton J et al (2015) The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nat Genet 47(4):330\u2013337","journal-title":"Nat Genet"},{"key":"5387_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.917125","volume":"10","author":"O Arnold","year":"2022","unstructured":"Arnold O, Barbosa K, Deshpande AJ, Zhu N (2022) The role of DOT1L in normal and malignant hematopoiesis. Front Cell Dev Biol 10:917125","journal-title":"Front Cell Dev Biol"},{"issue":"13","key":"5387_CR4","doi-asserted-by":"publisher","first-page":"3232","DOI":"10.1080\/10428194.2022.2116934","volume":"63","author":"BJ Ball","year":"2022","unstructured":"Ball BJ, Arslan S, Koller P, Ngo D, Afkhami M, Salhotra A, Al-Malki M, Aribi A, Ali H, Sandhu K et al (2022) Clinical experience with Venetoclax and hypomethylating agents (HMA) in patients with newly diagnosed and relapsed or refractory KMT2A-rearranged acute myeloid leukemia (AML). Leuk Lymphoma 63(13):3232\u20133236","journal-title":"Leuk Lymphoma"},{"issue":"1","key":"5387_CR5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.ccr.2011.06.009","volume":"20","author":"SR Daigle","year":"2011","unstructured":"Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J, Johnston LD, Scott MP, Smith JJ, Xiao Y et al (2011) Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 20(1):53\u201365","journal-title":"Cancer Cell"},{"issue":"1","key":"5387_CR6","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/bjh.14275","volume":"180","author":"P Diamanti","year":"2018","unstructured":"Diamanti P, Cox CV, Moppett JP, Blair A (2018) Dual targeting of Hsp90 in childhood acute lymphoblastic leukaemia. Br J Haematol 180(1):147\u2013149","journal-title":"Br J Haematol"},{"issue":"25","key":"5387_CR7","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1200\/JCO.20.03736","volume":"39","author":"CD DiNardo","year":"2021","unstructured":"DiNardo CD, Lachowiez CA, Takahashi K, Loghavi S, Xiao L, Kadia T, Daver N, Adeoti M, Short NJ, Sasaki K et al (2021) Venetoclax combined with FLAG-IDA induction and consolidation in newly diagnosed and relapsed or refractory acute myeloid leukemia. J Clin Oncol 39(25):2768\u20132778","journal-title":"J Clin Oncol"},{"key":"5387_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14194710","author":"J Dong","year":"2022","unstructured":"Dong J, Zhong T, Xu Z, Chen H, Wang X, Yang L, Lou Z, Xu Y, Hou T, Xu R et al (2022) Identification of Monobenzone as a novel potential anti-acute myeloid leukaemia agent that inhibits RNR and suppresses tumour growth in mouse xenograft model. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers14194710","journal-title":"Cancers (Basel)"},{"issue":"12","key":"5387_CR9","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/S0960-9822(02)00901-6","volume":"12","author":"Q Feng","year":"2002","unstructured":"Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, Zhang Y (2002) Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr Biol 12(12):1052\u20131058","journal-title":"Curr Biol"},{"key":"5387_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910658","author":"P Gorombei","year":"2021","unstructured":"Gorombei P, Guidez F, Ganesan S, Chiquet M, Pellagatti A, Goursaud L, Tekin N, Beurlet S, Patel S, Guerenne L et al (2021) BCL-2 inhibitor ABT-737 effectively targets leukemia-initiating cells with differential regulation of relevant genes leading to extended survival in a NRAS\/BCL-2 mouse model of high risk-myelodysplastic syndrome. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms221910658","journal-title":"Int J Mol Sci"},{"issue":"3","key":"5387_CR11","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nchembio.773","volume":"8","author":"J Grembecka","year":"2012","unstructured":"Grembecka J, He S, Shi A, Purohit T, Muntean AG, Sorenson RJ, Showalter HD, Murai MJ, Belcher AM, Hartley T et al (2012) Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nat Chem Biol 8(3):277\u2013284","journal-title":"Nat Chem Biol"},{"issue":"19","key":"5387_CR12","doi-asserted-by":"publisher","first-page":"5527","DOI":"10.1182\/bloodadvances.2020003490","volume":"6","author":"T Katsumoto","year":"2022","unstructured":"Katsumoto T, Ogawara Y, Yamagata K, Aikawa Y, Goitsuka R, Nakamura T, Kitabayashi I (2022) MOZ is critical for the development of MOZ\/MLL fusion-induced leukemia through regulation of Hoxa9\/Meis1 expression. Blood Adv 6(19):5527\u20135537","journal-title":"Blood Adv"},{"key":"5387_CR13","doi-asserted-by":"publisher","DOI":"10.3390\/cimb47030173","author":"M Kivrak","year":"2025","unstructured":"Kivrak M, Nalkiran I, Nalkiran SH (2025) Exploring the therapeutic potential of the DOT1L inhibitor EPZ004777 using bioinformatics and molecular docking approaches in acute myeloid leukemia. Curr Issues Mol Biol. https:\/\/doi.org\/10.3390\/cimb47030173","journal-title":"Curr Issues Mol Biol"},{"issue":"6","key":"5387_CR14","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.ccell.2019.11.001","volume":"36","author":"AV Krivtsov","year":"2019","unstructured":"Krivtsov AV, Evans K, Gadrey JY, Eschle BK, Hatton C, Uckelmann HJ, Ross KN, Perner F, Olsen SN, Pritchard T et al (2019) A menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia. Cancer Cell 36(6):660-673.e611","journal-title":"Cancer Cell"},{"issue":"10","key":"5387_CR15","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1158\/2159-8290.CD-16-0237","volume":"6","author":"MW K\u00fchn","year":"2016","unstructured":"K\u00fchn MW, Song E, Feng Z, Sinha A, Chen CW, Deshpande AJ, Cusan M, Farnoud N, Mupo A, Grove C et al (2016) Targeting chromatin regulators inhibits leukemogenic gene expression in NPM1 mutant leukemia. Cancer Discov 6(10):1166\u20131181","journal-title":"Cancer Discov"},{"key":"5387_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11060463","author":"M Lasica","year":"2021","unstructured":"Lasica M, Anderson MA (2021) Review of venetoclax in CLL, AML and multiple myeloma. J Pers Med. https:\/\/doi.org\/10.3390\/jpm11060463","journal-title":"J Pers Med"},{"issue":"354","key":"5387_CR17","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf5309","volume":"8","author":"JT Leonard","year":"2016","unstructured":"Leonard JT, Rowley JS, Eide CA, Traer E, Hayes-Lattin B, Loriaux M, Spurgeon SE, Druker BJ, Tyner JW, Chang BH (2016) Targeting BCL-2 and ABL\/LYN in Philadelphia chromosome-positive acute lymphoblastic leukemia. Sci Transl Med 8(354):354ra114","journal-title":"Sci Transl Med"},{"issue":"4","key":"5387_CR18","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1158\/2159-8290.CD-19-0710","volume":"10","author":"S Pei","year":"2020","unstructured":"Pei S, Pollyea DA, Gustafson A, Stevens BM, Minhajuddin M, Fu R, Riemondy KA, Gillen AE, Sheridan RM, Kim J et al (2020) Monocytic subclones confer resistance to Venetoclax-based therapy in patients with acute myeloid leukemia. Cancer Discov 10(4):536\u2013551","journal-title":"Cancer Discov"},{"issue":"7954","key":"5387_CR19","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/s41586-023-05755-9","volume":"615","author":"F Perner","year":"2023","unstructured":"Perner F, Stein EM, Wenge DV, Singh S, Kim J, Apazidis A, Rahnamoun H, Anand D, Marinaccio C, Hatton C et al (2023) MEN1 mutations mediate clinical resistance to menin inhibition. Nature 615(7954):913\u2013919","journal-title":"Nature"},{"issue":"12","key":"5387_CR20","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1038\/leu.2015.143","volume":"29","author":"A Pigneux","year":"2015","unstructured":"Pigneux A, Labopin M, Maertens J, Cordonnier C, Volin L, Soci\u00e9 G, Blaise D, Craddock C, Milpied N, Bacher U et al (2015) Outcome of allogeneic hematopoietic stem-cell transplantation for adult patients with AML and 11q23\/MLL rearrangement (MLL-r AML). Leukemia 29(12):2375\u20132381","journal-title":"Leukemia"},{"issue":"1","key":"5387_CR21","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/emmm.201201703","volume":"5","author":"K Rehe","year":"2013","unstructured":"Rehe K, Wilson K, Bomken S, Williamson D, Irving J, den Boer ML, Stanulla M, Schrappe M, Hall AG, Heidenreich O et al (2013) Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations. EMBO Mol Med 5(1):38\u201351","journal-title":"EMBO Mol Med"},{"issue":"2","key":"5387_CR22","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/ijc.2910260208","volume":"26","author":"S Tsuchiya","year":"1980","unstructured":"Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T, Tada K (1980) Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer 26(2):171\u2013176","journal-title":"Int J Cancer"},{"issue":"1","key":"5387_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03009-4","volume":"5","author":"Y Wang","year":"2022","unstructured":"Wang Y, Huo T, Tseng YJ, Dang L, Yu Z, Yu W, Foulks Z, Murdaugh RL, Ludtke SJ, Nakada D et al (2022) Using Cryo-ET to distinguish platelets during pre-acute myeloid leukemia from steady state hematopoiesis. Commun Biol 5(1):72","journal-title":"Commun Biol"},{"key":"5387_CR24","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.584974","volume":"10","author":"Y Wei","year":"2020","unstructured":"Wei Y, Cao Y, Sun R, Cheng L, Xiong X, Jin X, He X, Lu W, Zhao M (2020) Targeting Bcl-2 proteins in acute myeloid leukemia. Front Oncol 10:584974","journal-title":"Front Oncol"},{"issue":"2","key":"5387_CR25","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.stemcr.2021.12.004","volume":"17","author":"CK Wille","year":"2022","unstructured":"Wille CK, Sridharan R (2022) DOT1L inhibition enhances pluripotency beyond acquisition of epithelial identity and without immediate suppression of the somatic transcriptome. Stem Cell Reports 17(2):384\u2013396","journal-title":"Stem Cell Reports"},{"issue":"1","key":"5387_CR26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13045-022-01251-1","volume":"15","author":"Y Yi","year":"2022","unstructured":"Yi Y, Ge S (2022) Targeting the histone H3 lysine 79 methyltransferase DOT1L in MLL-rearranged leukemias. J Hematol Oncol 15(1):35","journal-title":"J Hematol Oncol"},{"issue":"4","key":"5387_CR27","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.7150\/jca.91892","volume":"15","author":"J Zhou","year":"2024","unstructured":"Zhou J, Chen C (2024) Suppression of malignant melanoma by knocking down growth differentiation factor-15 via inhibiting PTEN\/PI3K\/AKT signaling pathway. J Cancer 15(4):1115\u20131123","journal-title":"J Cancer"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05387-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-026-05387-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05387-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T03:04:23Z","timestamp":1784775863000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-026-05387-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["5387"],"URL":"https:\/\/doi.org\/10.1007\/s00210-026-05387-6","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"assertion":[{"value":"14 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments were conducted in accordance with the guidelines and with the approval of the Institutional Animal Ethics Committee of The Second Hospital of Hebei Medical University (No.2023-AE095). Furthermore, all animal euthanasia procedures strictly adhered to the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}