{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:52:16Z","timestamp":1781855536360,"version":"3.54.5"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Leukemia, a hematological malignancy resulting from genetic mutations and environmental factors, leads to uncontrolled proliferation and impaired differentiation of hematopoietic cells. Current treatment modalities face limitations such as drug resistance and off\u2010target toxicity, highlighting the need for novel therapeutic strategies. This study evaluates the individual and fixed\u2010dose combined in vitro effects of boric acid (BA) and Myeloid Ecotropic Viral Integration Site 1 Inhibitor\u20102 (Meis1i\u20102) in leukemia cell lines, focusing on apoptosis, cell\u2010cycle distribution, and selected transcript\u2010level changes. Three distinct leukemia cell lines (K562, RS4\u201011, CCRF\u2010CEM) were cultured under standardized conditions and treated with varying concentrations of BA and Meis1i\u20102 individually and in combination. Apoptotic cell death was evaluated using flow cytometry\u2010based Annexin V\u2013FITC\/PI staining, while cell cycle dynamics were assessed via Hoechst 33342 and Pyronin Y staining followed by flow cytometric analysis. Additionally, quantitative RT\u2010PCR (qRT\u2010PCR) was employed to determine the expression levels of apoptosis\u2010related and cell cycle regulatory genes. At the 72\u2010h endpoint, BA and Meis1i\u20102 produced measurable changes in viability, apoptosis, and cell\u2010cycle distribution in a cell\u2010line\u2010 and concentration\u2010dependent manner. The high\u2010dose fixed combination of BA (2000\u2009\u00b5M) and Meis1i\u20102 (10\u2009\u00b5M) reduced viability compared with DMSO controls in several assays; however, this condition was above the RS4\u201011 IC\n                    <jats:sub>50<\/jats:sub>\n                    values and should be interpreted as a supra\u2010IC\n                    <jats:sub>50<\/jats:sub>\n                    exploratory condition rather than evidence of superiority over the most active single agent. Annexin V\/PI and cell\u2010cycle analyses showed treatment\u2010associated apoptotic changes and redistribution of G1, S, and G2\/M phases depending on the cell line. Targeted qRT\u2010PCR indicated transcript\u2010level modulation of selected apoptosis\u2010 and cell\u2010cycle\u2010related genes, but these changes were not uniform across all models. These findings reveal that BA and Meis1i\u20102 exhibit biologically measurable antileukemic effects through apoptosis induction and cell cycle modulation. However, Chou\u2010Talalay analysis in RS4\u201011 cells yielded CI values greater than 1 at the tested concentrations, suggesting an antagonistic rather than non\u2010synergistic under the tested conditions. Therefore, under the current experimental conditions, the combination demonstrates concentration\u2010specific antileukemic activity rather than pharmacological interaction. Future studies using expanded sub\u2010IC\n                    <jats:sub>50<\/jats:sub>\n                    dose matrices, protein\u2010level and functional validation, and in vivo models are required.\n                  <\/jats:p>","DOI":"10.1002\/cbin.70171","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:17:20Z","timestamp":1780319840000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell Line\u2010Specific In Vitro Effects of Boric Acid and Meis1i\u20102 in Leukemia Cells: Apoptosis, Cell\u2010Cycle Modulation, and Fixed\u2010Dose Interaction"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-5052","authenticated-orcid":false,"given":"Neslihan","family":"Meri\u00e7","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences K\u00fctahya Health Sciences University K\u00fctahya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0569-9482","authenticated-orcid":false,"given":"Aynura","family":"Mammadova","sequence":"additional","affiliation":[{"name":"Department of Genetics and Bioengineering, Faculty of Engineering Yeditepe University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Kocaba\u015f","sequence":"additional","affiliation":[{"name":"Department of Genetics and Bioengineering, Faculty of Engineering Yeditepe University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8356-9806","authenticated-orcid":false,"given":"Fatih","family":"Kar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine K\u00fctahya Health Sciences University K\u00fctahya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30466"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e33665"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CANLET.2004.06.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jdb9040044"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3858-3_4"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-014-9755-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1947"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4274\/meandros.galenos.2020.82246"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.46810\/tdfd.995903"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.05.026"},{"issue":"4","key":"e_1_2_10_12_1","first-page":"182","article-title":"Kanser Tedavisinde Proteozom Inhibit\u00f6rlerinin \u00d6nemi. 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