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The <jats:italic>FAT1<\/jats:italic> gene is mutated in 12\u201316% of T-cell acute leukemia (T-ALL) and aberrantly expressed in about 54% of T-ALL cases contrasted with absent expression in normal T-cells. Here, we characterized <jats:italic>FAT1<\/jats:italic> expression and profiled the methylation status from T-ALL patients. In our T-ALL cohort, 53% of patient samples were <jats:italic>FAT1<\/jats:italic> positive (FAT1pos) compared to only 16% <jats:italic>FAT1<\/jats:italic> positivity in early T-ALL patient samples. Aberrant expression of <jats:italic>FAT1<\/jats:italic> was strongly associated with <jats:italic>FAT1<\/jats:italic> promotor hypomethylation, yet a subset, mainly consisting of TLX1-driven T-ALL patient samples showed methylation-independent high <jats:italic>FAT1<\/jats:italic> expression. Genes correlating with <jats:italic>FAT1<\/jats:italic> expression revealed enrichment in WNT signaling genes representing the most enriched single pathway. <jats:italic>FAT1<\/jats:italic> knockdown or knockout led to impaired proliferation and downregulation of WNT pathway target genes (<jats:italic>CCND1<\/jats:italic>, <jats:italic>MYC<\/jats:italic>, <jats:italic>LEF1)<\/jats:italic>, while <jats:italic>FAT1<\/jats:italic> overexpressing conveyed a proliferative advantage. To conclude, we characterized a subtype pattern of <jats:italic>FAT1<\/jats:italic> gene expression in adult T-ALL patients correlating with promotor methylation status. <jats:italic>FAT1<\/jats:italic> dependent proliferation and WNT signaling discloses an impact on deeper understanding of T-ALL leukemogenesis as a fundament for prospective therapeutic strategies.<\/jats:p>","DOI":"10.1038\/s41598-023-27792-0","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T12:03:04Z","timestamp":1674043384000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["FAT1 expression in T-cell acute lymphoblastic leukemia (T-ALL) modulates proliferation and WNT signaling"],"prefix":"10.1038","volume":"13","author":[{"given":"Sven","family":"Liebig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Ortiz-Tanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstandina","family":"Isaakidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Schlee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Schroeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Beder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc G. 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E. & Thorne, R. F. Sleeping giants: Emerging roles for the fat cadherins in health and disease. Med. Res. Rev. 34, 190\u2013221. https:\/\/doi.org\/10.1002\/med.21286 (2014).","journal-title":"Med. Res. Rev."},{"key":"27792_CR2","doi-asserted-by":"publisher","first-page":"8579","DOI":"10.1073\/pnas.0811691106","volume":"106","author":"K Skouloudaki","year":"2009","unstructured":"Skouloudaki, K. et al. Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development. Proc. Natl. Acad. Sci. USA 106, 8579\u20138584. https:\/\/doi.org\/10.1073\/pnas.0811691106 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"27792_CR3","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1242\/dev.01254","volume":"131","author":"H Matakatsu","year":"2004","unstructured":"Matakatsu, H. & Blair, S. S. Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing. 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