{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:03:45Z","timestamp":1752192225609,"version":"3.41.2"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"DOI":"10.1007\/s12672-025-03036-7","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T07:27:23Z","timestamp":1751959643000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting WEE1 and asciminib suppresses ABL-tyrosine kinase inhibitor-resistant chronic myeloid leukemia cells"],"prefix":"10.1007","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2727-658X","authenticated-orcid":false,"given":"Seiichi","family":"Okabe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuru","family":"Moriyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Gotoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daigo","family":"Akahane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"3036_CR1","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1002\/ajh.25792","volume":"95","author":"E Jabbour","year":"2020","unstructured":"Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy, and monitoring. Am J Hematol. 2020;95:691\u2013709.","journal-title":"Am J Hematol"},{"key":"3036_CR2","doi-asserted-by":"publisher","first-page":"100968","DOI":"10.1016\/j.blre.2022.100968","volume":"56","author":"JH Lipton","year":"2022","unstructured":"Lipton JH, Br\u00fcmmendorf TH, Gambacorti-Passerini C, Garcia-Guti\u00e9rrez V, Deininger MW, Cortes JE. Long-term safety review of tyrosine kinase inhibitors in chronic myeloid leukemia\u2014what to look for when treatment-free remission is not an option. Blood Rev. 2022;56:100968.","journal-title":"Blood Rev"},{"key":"3036_CR3","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/s41408-023-00823-9","volume":"13","author":"J Senapati","year":"2023","unstructured":"Senapati J, Sasaki K, Issa GC, Lipton JH, Radich JP, Jabbour E, et al. Management of chronic myeloid leukemia in 2023\u2014common ground and common sense. Blood Cancer J. 2023;13:58.","journal-title":"Blood Cancer J"},{"key":"3036_CR4","doi-asserted-by":"publisher","first-page":"5116","DOI":"10.3390\/cancers13205116","volume":"13","author":"T Ono","year":"2021","unstructured":"Ono T. Which tyrosine kinase inhibitors should be selected as the first-line treatment for chronic myelogenous leukemia in the chronic phase? Cancers (Basel). 2021;13:5116.","journal-title":"Cancers (Basel)"},{"key":"3036_CR5","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13045-021-01055-9","volume":"14","author":"J Cortes","year":"2021","unstructured":"Cortes J, Lang F. Third-line therapy for chronic myeloid leukemia: current status and future directions. J Hematol Oncol. 2021;14:44.","journal-title":"J Hematol Oncol"},{"key":"3036_CR6","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.3324\/haematol.2022.282361","volume":"108","author":"S Padala","year":"2023","unstructured":"Padala S, Cortes J. Asciminib in chronic myeloid leukemia: a STAMP for expedited delivery? Haematologica. 2023;108:2913\u20138.","journal-title":"Haematologica"},{"issue":"Suppl 1","key":"3036_CR7","doi-asserted-by":"publisher","first-page":"S29","DOI":"10.5045\/br.2023.2023017","volume":"58","author":"EJ Choi","year":"2023","unstructured":"Choi EJ. Asciminib: the first-in-class allosteric inhibitor of BCR::ABL1 kinase. Blood Res. 2023;58(Suppl 1):S29\u201336.","journal-title":"Blood Res"},{"key":"3036_CR8","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s13045-020-00959-2","volume":"13","author":"A Cerchione","year":"2020","unstructured":"Ghelli Luserna di Ror\u00e0, Cerchione A, Martinelli C, Simonetti G. A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target. J Hematol Oncol. 2020;13:126.","journal-title":"J Hematol Oncol"},{"key":"3036_CR9","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/d41573-019-00202-9","volume":"19","author":"CRM Asquith","year":"2020","unstructured":"Asquith CRM, Laitinen T, East MP. PKMYT1: a forgotten member of the WEE1 family. Nat Rev Drug Discov. 2020;19:157.","journal-title":"Nat Rev Drug Discov"},{"key":"3036_CR10","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.3390\/molecules22122045","volume":"22","author":"M Schmidt","year":"2017","unstructured":"Schmidt M, Rohe A, Platzer C, Najjar A, Erdmann F, Sippl W. Regulation of G2\/M transition by inhibiting WEE1 and PKMYT1 kinases. Molecules. 2017;22:2045.","journal-title":"Molecules"},{"key":"3036_CR11","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.3390\/cells12111471","volume":"12","author":"YL Su","year":"2023","unstructured":"Su YL, Xiao LY, Huang SY, Wu CC, Chang LC, Chen YH, et al. Inhibiting WEE1 augments the antitumor efficacy of cisplatin in urothelial carcinoma by enhancing the DNA damage process. Cells. 2023;12:1471.","journal-title":"Cells"},{"key":"3036_CR12","doi-asserted-by":"publisher","first-page":"901132","DOI":"10.3389\/fonc.2022.901132","volume":"12","author":"M Mancini","year":"2022","unstructured":"Mancini M, De Santis S, Monaldi C, Castagnetti F, Lonetti A, Bruno S, et al. Polo-like kinase-1, Aurora kinase A, and WEE1 kinase are promising druggable targets in CML cells displaying BCR::ABL1-independent resistance to tyrosine kinase inhibitors. Front Oncol. 2022;12:901132. https:\/\/doi.org\/10.3389\/fonc.2022.901132.","journal-title":"Front Oncol"},{"key":"3036_CR13","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s12964-022-01021-z","volume":"20","author":"F Zeng","year":"2022","unstructured":"Zeng F, Peng Y, Qin Y, Wang J, Jiang G, Feng W, et al. Wee1 promotes cell proliferation and Imatinib resistance in chronic myeloid leukemia via regulating DNA damage repair dependent on ATM-gammaH2AX-MDC1. Cell Commun Signal. 2022;20:199. https:\/\/doi.org\/10.1186\/s12964-022-01021-z.","journal-title":"Cell Commun Signal"},{"key":"3036_CR14","doi-asserted-by":"publisher","first-page":"101521","DOI":"10.1016\/j.xcrm.2024.101521","volume":"5","author":"S Adnan Awad","year":"2024","unstructured":"Adnan Awad S, Dufva O, Klievink J, Karjalainen E, Ianevski A, Pietarinen P, et al. Integrated drug profiling and CRISPR screening identify BCR::ABL1-independent vulnerabilities in chronic myeloid leukemia. Cell Rep Med. 2024;5:101521. https:\/\/doi.org\/10.1016\/j.xcrm.2024.101521.","journal-title":"Cell Rep Med"},{"key":"3036_CR15","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1080\/10428194.2019.1660971","volume":"61","author":"S Okabe","year":"2020","unstructured":"Okabe S, Tanaka Y, Moriyama M, Gotoh A. Efficacy of dasatinib against ponatinib-resistant chronic myeloid leukemia cells. Leuk Lymphoma. 2020;61:237\u20139.","journal-title":"Leuk Lymphoma"},{"key":"3036_CR16","doi-asserted-by":"publisher","first-page":"3948","DOI":"10.1182\/blood-2005-06-2209","volume":"106","author":"S Kimura","year":"2005","unstructured":"Kimura S, Naito H, Segawa H, Kuroda J, Yuasa T, Sato K, et al. NS-187, a potent and selective dual Bcr-Abl\/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia. Blood. 2005;106:3948\u201354.","journal-title":"Blood"},{"key":"3036_CR17","doi-asserted-by":"publisher","first-page":"6181","DOI":"10.1158\/1078-0432.CCR-08-0461","volume":"14","author":"S Okabe","year":"2008","unstructured":"Okabe S, Tauchi T, Ohyashiki K. Characteristics of dasatinib- and imatinib-resistant chronic myelogenous leukemia cells. Clin Cancer Res. 2008;14:6181\u20136. https:\/\/doi.org\/10.1158\/1078-0432.CCR-08-0461.","journal-title":"Clin Cancer Res"},{"key":"3036_CR18","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.jare.2020.04.016","volume":"24","author":"SQ Li","year":"2020","unstructured":"Li SQ, Liu J, Zhang J, Wang XL, Chen D, Wang Y, et al. Transcriptome profiling reveals the high incidence of hnRNPA1 exon 8 inclusion in chronic myeloid leukemia. J Adv Res. 2020;24:301\u201310.","journal-title":"J Adv Res"},{"key":"3036_CR19","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1182\/blood-2013-05-501072","volume":"122","author":"K Cramer-Morales","year":"2013","unstructured":"Cramer-Morales K, Nieborowska-Skorska M, Scheibner K, Padget M, Irvine DA, Sliwinski T, et al. Personalized synthetic lethality induced by targeting RAD52 in leukemias identified by gene mutation and expression profile. Blood. 2013;122:1293\u2013304. PMID: 23836560.","journal-title":"Blood"},{"key":"3036_CR20","doi-asserted-by":"crossref","unstructured":"Prieto C, Barrios D. RaNA-Seq: interactive RNA-Seq analysis from FASTQ files to functional analysis. Bioinformatics. 2020;36:1955\u20131956.","DOI":"10.1093\/bioinformatics\/btz854"},{"key":"3036_CR21","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/s41588-021-00828-9","volume":"53","author":"D Inoue","year":"2021","unstructured":"Inoue D, Polaski JT, Taylor J, Castel P, Chen S, Kobayashi S, et al. Minor intron retention drives clonal hematopoietic disorders and diverse cancer predisposition. Nat Genet. 2021;53:707\u201318.","journal-title":"Nat Genet"},{"key":"3036_CR22","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/s12935-023-02961-3","volume":"23","author":"S Okabe","year":"2023","unstructured":"Okabe S, Tanaka Y, Moriyama M, Gotoh A. WEE1 and PARP-1 play critical roles in myelodysplastic syndrome and acute myeloid leukemia treatment. Cancer Cell Int. 2023;23:128. https:\/\/doi.org\/10.1186\/s12935-023-02961-3.","journal-title":"Cancer Cell Int"},{"issue":"3","key":"3036_CR23","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s00277-018-3547-7","volume":"98","author":"S Okabe","year":"2019","unstructured":"Okabe S, Tanaka Y, Tauchi T, Ohyashiki K. Copanlisib, a novel phosphoinositide 3-kinase inhibitor, combined with Carfilzomib inhibits multiple myeloma cell proliferation. Ann Hematol. 2019;98(3):723\u201333. https:\/\/doi.org\/10.1007\/s00277-018-3547-7.","journal-title":"Ann Hematol"},{"key":"3036_CR24","doi-asserted-by":"publisher","first-page":"339","DOI":"10.15171\/apb.2017.041","volume":"7","author":"B Mansoori","year":"2017","unstructured":"Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull. 2017;7:339\u201348.","journal-title":"Adv Pharm Bull"},{"key":"3036_CR25","first-page":"141","volume":"2","author":"X Wang","year":"2019","unstructured":"Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist. 2019;2:141\u201360.","journal-title":"Cancer Drug Resist"},{"key":"3036_CR26","doi-asserted-by":"publisher","first-page":"7519","DOI":"10.1158\/1078-0432.CCR-09-1068","volume":"15","author":"D Milojkovic","year":"2009","unstructured":"Milojkovic D, Apperley J. Mechanisms of resistance to Imatinib and second-generation tyrosine inhibitors in chronic myeloid leukemia. Clin Cancer Res. 2009;15:7519\u201327.","journal-title":"Clin Cancer Res"},{"issue":"1","key":"3036_CR27","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/s41467-024-44771-9","volume":"15","author":"MT Scott","year":"2024","unstructured":"Scott MT, Liu W, Mitchell R, Clarke CJ, et al. Activating p53 abolishes self-renewal of quiescent leukaemic stem cells in residual CML disease. Nat Commun. 2024;15(1):651.","journal-title":"Nat Commun"},{"key":"3036_CR28","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1056\/NEJMoa1902328","volume":"381","author":"TP Hughes","year":"2019","unstructured":"Hughes TP, Mauro MJ, Cortes JE, Minami H, Rea D, DeAngelo DJ, et al. Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure. N Engl J Med. 2019;381:2315\u201326. https:\/\/doi.org\/10.1056\/NEJMoa1902328.","journal-title":"N Engl J Med"},{"key":"3036_CR29","doi-asserted-by":"publisher","first-page":"3409","DOI":"10.1200\/JCO.2014.60.4009","volume":"33","author":"K Do","year":"2015","unstructured":"Do K, Wilsker D, Ji J, Zlott J, Freshwater T, Kinders RJ, et al. Phase I study of single-agent AZD1775 (MK-1775), a Wee1 kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol. 2015;33:3409\u201315. https:\/\/doi.org\/10.1200\/JCO.2014.60.4009.","journal-title":"J Clin Oncol"},{"key":"3036_CR30","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.ab.2017.07.009","volume":"552","author":"LD Zorova","year":"2018","unstructured":"Zorova LD, Popkov VA, Plotnikov EY, Silachev DN, Pevzner IB, Jankauskas SS, et al. Mitochondrial membrane potential. Anal Biochem. 2018;552:50\u20139.","journal-title":"Anal Biochem"},{"key":"3036_CR31","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1007\/s10495-022-01735-y","volume":"27","author":"S Kari","year":"2022","unstructured":"Kari S, Subramanian K, Altomonte IA, Murugesan A, Yli-Harja O, Kandhavelu M. Programmed cell death detection methods: a systematic review and a categorical comparison. Apoptosis. 2022;27:482\u2013508.","journal-title":"Apoptosis"},{"issue":"10","key":"3036_CR32","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1056\/NEJMoa2400858","volume":"391","author":"A Hochhaus","year":"2024","unstructured":"Hochhaus A, Wang J, Kim DW, Kim DDH, Mayer J, Goh YT, le Coutre P, Takahashi N, Kim I, Etienne G, Andorsky D, Issa GC, Larson RA, Bombaci F, Kapoor S, McCulloch T, Malek K, Yau L, Ifrah S, Hoch M, Cortes JE, Hughes TP. ASC4FIRST investigators. Asciminib in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2024;391(10):885\u201398. https:\/\/doi.org\/10.1056\/NEJMoa2400858.","journal-title":"N Engl J Med"},{"key":"3036_CR33","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.ygyno.2023.05.063","volume":"174","author":"A Embaby","year":"2023","unstructured":"Embaby A, Kutzera J, Geenen JJ, Pluim D, Hofland I, Sanders J, et al. WEE1 inhibitor Adavosertib in combination with carboplatin in advanced TP53-mutated ovarian cancer: a biomarker-enriched phase II study. Gynecol Oncol. 2023;174:239\u201346.","journal-title":"Gynecol Oncol"},{"key":"3036_CR34","doi-asserted-by":"publisher","first-page":"9930","DOI":"10.1038\/s41598-020-66018-5","volume":"10","author":"DH Ha","year":"2020","unstructured":"Ha DH, Min A, Kim S, Jang H, Kim SH, Kim HJ, et al. Antitumor effect of a WEE1 inhibitor and potentiation of Olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer. Sci Rep. 2020;10:9930.","journal-title":"Sci Rep"},{"key":"3036_CR35","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1158\/1535-7163.MCT-13-0025","volume":"12","author":"AD Guertin","year":"2013","unstructured":"Guertin AD, Li J, Liu Y, Hurd MS, Schuller AG, Long B, et al. Preclinical evaluation of the WEE1 inhibitor MK-1775 as single-agent anticancer therapy. Mol Cancer Ther. 2013;12:1442\u201352.","journal-title":"Mol Cancer Ther"},{"key":"3036_CR36","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1200\/JCO.22.00830","volume":"41","author":"S Fu","year":"2023","unstructured":"Fu S, Yao S, Yuan Y, Previs RA, Elias AD, Carvajal RD, et al. Multicenter phase II trial of the WEE1 inhibitor Adavosertib in refractory solid tumors harboring CCNE1 amplification. J Clin Oncol. 2023;41:1725\u201334.","journal-title":"J Clin Oncol"},{"key":"3036_CR37","doi-asserted-by":"publisher","first-page":"49902","DOI":"10.18632\/oncotarget.10231","volume":"7","author":"HY Kim","year":"2016","unstructured":"Kim HY, Cho Y, Kang H, Yim YS, Kim SJ, Song J, et al. Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer. Oncotarget. 2016;7:49902\u201316.","journal-title":"Oncotarget"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-03036-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-025-03036-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-03036-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:18:24Z","timestamp":1752139104000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-025-03036-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3036"],"URL":"https:\/\/doi.org\/10.1007\/s12672-025-03036-7","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]},"assertion":[{"value":"28 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 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":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1283"}}