{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T22:28:53Z","timestamp":1783376933995,"version":"3.54.6"},"reference-count":185,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Saban Research Institute Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The Wnt signaling pathway plays a critical role in regulating normal hematopoiesis and immune cell development. However, its dysregulation has emerged as a key driver of leukemogenesis. Leukemic stem cells exploit aberrant Wnt signaling to sustain self-renewal, evade apoptosis, and promote unchecked proliferation. In this review, we highlight the dual roles of canonical and non-canonical Wnt pathways in acute leukemia, emphasizing their distinct and overlapping contributions to disease progression. We also evaluate current preclinical and clinical strategies targeting Wnt signaling, identifying both promising advances and persistent obstacles to therapeutic translation. By elucidating the molecular mechanisms underlying Wnt pathway dysregulation in leukemic cells, this review underscores the potential of Wnt-directed therapies as a novel class of interventions to improve outcomes for patients with acute leukemia.<\/jats:p>","DOI":"10.3390\/cancers17152456","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T14:11:44Z","timestamp":1753366304000},"page":"2456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting Wnt Signaling in Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6580-3379","authenticated-orcid":false,"given":"Samantha","family":"Hurwitz","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, Division of Hematology and Oncology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4740-9801","authenticated-orcid":false,"given":"Ki Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, Division of Hematology and Oncology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2057-4148","authenticated-orcid":false,"given":"Tatiana","family":"Fourfouris","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, Division of Hematology and Oncology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Choi","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, Division of Hematology and Oncology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishan","family":"Parikh","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, Division of Hematology and Oncology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Friedmann","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, Division of Hematology and Oncology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5716-4215","authenticated-orcid":false,"given":"Maiah","family":"Zarrabi","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, Division of Hematology and Oncology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3793-6438","authenticated-orcid":false,"given":"Yong-Mi","family":"Kim","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, Division of Hematology and Oncology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chiarini, F., Paganelli, F., Martelli, A.M., and Evangelisti, C. 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