{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T18:35:24Z","timestamp":1788028524789,"version":"build-2784847793"},"reference-count":115,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hematological malignancies, including multiple myeloma (MM), leukemia, and lymphoma, represent a major global health burden, accounting for approximately 6.6% of all cancer cases and contributing to significant mortality. The evolutionary conserved WNT\/\u03b2-catenin signaling pathway is a critical regulator of normal hematopoietic stem cell homeostasis, and its dysregulation is a hallmark of various hematological malignancies. Aberrant activation through mutations, overexpression of ligands, or disruption of the destruction complex drives uncontrolled proliferation, impaired differentiation, and therapeutic resistance to therapy in acute and chronic leukemias, lymphomas, and multiple myeloma. Therapeutic interventions targeting this pathway, such as GSK-3 inhibitors, \u03b2-catenin antagonists, and small molecules like CWP291 and salinomycin, have demonstrated promising antitumor effects. Furthermore, combining WNT\/\u03b2-catenin inhibition with targeted or epigenetic therapies, such as venetoclax and chidamide, can produce synergistic antitumor effects and overcome chemoresistance. Despite this potential, clinical translation is hampered by on-target toxicities in healthy tissues, pathway complexity, and a lack of predictive biomarkers. We conclude that the future of WNT-directed therapy lies in developing biomarker-selective agents, advanced drug delivery systems to improve specificity, and exploring novel combinations with immunotherapy to harness the anti-tumor immune response.<\/jats:p>","DOI":"10.3390\/biom16050653","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:34:42Z","timestamp":1777458882000},"page":"653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the WNT\/\u03b2-Catenin Pathway in Hematological Malignancies: From Molecular Pathogenesis to Emerging Therapeutic Strategies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3533-468X","authenticated-orcid":false,"given":"Ali","family":"Keyhani","sequence":"first","affiliation":[{"name":"Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3395-654X","authenticated-orcid":false,"given":"Hamed","family":"Haddad Kashani","sequence":"additional","affiliation":[{"name":"Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadijeh","family":"Dizaji Asl","sequence":"additional","affiliation":[{"name":"Department of Histopathology and Anatomy, TaMS.C., Islamic Azad University, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Mazloumi","sequence":"additional","affiliation":[{"name":"Department of Medical Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faride","family":"Kaikavoosnejad","sequence":"additional","affiliation":[{"name":"Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2225-5710","authenticated-orcid":false,"given":"Seyyede Sepide","family":"Ashraf Moosavi","sequence":"additional","affiliation":[{"name":"Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milad","family":"Verdi","sequence":"additional","affiliation":[{"name":"Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-2906","authenticated-orcid":false,"given":"Ali","family":"Rafat","sequence":"additional","affiliation":[{"name":"Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-156X","authenticated-orcid":false,"given":"Reza","family":"Nejati","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s40364-022-00418-9","article-title":"The Wnt\/\u03b2-catenin signalling pathway in Haematological Neoplasms","volume":"10","author":"Yu","year":"2022","journal-title":"Biomark. 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