{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T12:28:48Z","timestamp":1782390528311,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Innovation"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Chronic myeloid leukemia (CML) is a clonal malignancy propelled by the\n                      <jats:italic>BCR::ABL1<\/jats:italic>\n                      fusion gene originating from the Philadelphia chromosome. This gene activates ABL tyrosine kinase, which enhances the survival of leukemic cells. Although tyrosine kinase inhibitors (TKIs) have significantly advanced the treatment of CML, resistance to these inhibitors presents a substantial hurdle. Consequently, novel therapeutic strategies targeting resistance mechanisms independent of\n                      <jats:italic>BCR::ABL1<\/jats:italic>\n                      are urgently needed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigated the potential impact of combining WEE1 inhibitors, particularly MK\u20101775, with vitamin K2 (VK2) in treating CML. To analyze differentially expressed and spliced transcripts in CML, we examined mRNA profiles from peripheral blood mononuclear cells of five patients with CML (during chronic and blast phases) and five healthy controls. The samples were analyzed using deep sequencing. Differential expression analyses were performed using RaNA\u2010Seq and Heatmapper, the latter of which was designed for complex data set visualizations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WEE1 controls the G2\/M checkpoint to prevent early mitosis, and blocking it increases the cytotoxicity of agents that damage deoxyribonucleic acid, especially in cancers lacking p53. VK2, a micronutrient, exerts anticancer effects against various malignancies. Gene expression studies have indicated that PKMYT1 expression is elevated in CML but not WEE1 cells. MK\u20101775 successfully halted the growth of both standard and TKI\u2010resistant CML cell lines by triggering apoptosis via caspase 3\/7 activation. VK2 reduced the viability of CML cells and increased cytotoxicity. A combined regimen of MK\u20101775 and VK2 markedly decreased colony growth, disrupted mitochondrial membrane potential, and increased death in CML cells, including those resistant to TKIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results suggest that a combination of MK\u20101775 and VK2 represents a potentially effective treatment strategy for CML, especially in drug\u2010resistant cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cai2.70024","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T04:25:52Z","timestamp":1756441552000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Combination of WEE1 Inhibitor and Vitamin K2 Enhances Therapeutic Efficacy in Chronic Myeloid Leukemia"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2727-658X","authenticated-orcid":false,"given":"Seiichi","family":"Okabe","sequence":"first","affiliation":[{"name":"Department of Hematology Tokyo Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Hematology Tokyo Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Gotoh","sequence":"additional","affiliation":[{"name":"Department of Hematology Tokyo Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daigo","family":"Akahane","sequence":"additional","affiliation":[{"name":"Department of Hematology Tokyo Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v12.i2.69"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/243290a0"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25792"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.14694\/edbook_am.2015.35.e381"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14143300"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13205116"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2017.04.007"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910689"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.828684"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00959-2"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.mct-11-0529"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.3213"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14204219"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2209"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2019.1660971"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2010.04.017"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2020.04.016"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510423103"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz854"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw419"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-09-1947"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.11.040"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2017.07.009"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26225"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2024.100809"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2492"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-2959"}],"container-title":["Cancer 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