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Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The molecular mechanisms underlying chronic myeloid leukemia (CML) progression from chronic phase (CP) to blast crisis (BC) remain incompletely understood. This study aimed to identify progression-specific genes and elucidate the role of N-cadherin (CDH2) in BC transformation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the GSE4170 dataset to identify differentially expressed genes (DEGs) across CML phases. Functional annotations were performed via GSEA, GO, and KEGG analyses. The role of N-cadherin was validated using <jats:italic>in vitro<\/jats:italic> (KU812 cell line) and <jats:italic>in vivo<\/jats:italic> (nude mouse xenograft) models. The <jats:italic>\u03b2<\/jats:italic>-catenin inhibitor MSAB was employed for mechanistic studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transcriptomic analysis identified 1,294 DEGs during CML progression, with 41 \"progression-specific\" genes showing consistent expression trends. Among these, N-cadherin was significantly upregulated in BC patient samples. Overexpression of N-cadherin in KU812 cells promoted cell cycle entry, accelerated tumor growth <jats:italic>in vivo<\/jats:italic>, and suppressed the expression of granulocyte surface differentiation antigens. MSAB treatment effectively reversed these malignant phenotypes. Furthermore, CDH2 mRNA was notably upregulated in advanced-phase samples compared to chronic-phase samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings elucidate the role of CDH2 in CML progression through activation of the Wnt\/<jats:italic>\u03b2<\/jats:italic>-catenin signaling pathway. Targeting the N-cadherin\/<jats:italic>\u03b2<\/jats:italic>-catenin axis with MSAB may represent a novel therapeutic strategy for BC-CML.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1657508","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T04:17:45Z","timestamp":1760588265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the N-cadherin\/\u03b2-catenin axis with MSAB reverses malignant phenotypes in blast crisis of CML"],"prefix":"10.3389","volume":"15","author":[{"given":"Yingying","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songqin","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyi","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1196\/annals.1349.001","article-title":"Acute myeloid leukemia stem cells","volume":"1044","author":"Dick","year":"2005","journal-title":"Ann New York Acad 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