García Hernández, VioletaArambilet, DavidGuillén, YolandaLobo-Jarne, TeresaMaqueda, MariaGekas, ChristosGonzález, JessicaIglesias, ArnauVega García, NereaSentís Carreras, Inés 1990-Trincado Alonso, Juan Luis, 1987-Márquez-López, IanHeyn, HolgerCamós, MireiaEspinosa Blay, LluísBigas Salvans, Anna2023-03-062023-03-062023García-Hernández V, Arambilet D, Guillén Y, Lobo-Jarne T, Maqueda M, Gekas C, González J, Iglesias A, Vega-García N, Sentís I, Trincado JL, Márquez-López I, Heyn H, Camós M, Espinosa L, Bigas A. β-Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T-cell acute lymphoblastic leukemia. EMBO Mol Med. 2023 Feb 8;15(2):e16554. DOI: 10.15252/emmm.2022165541757-4676http://hdl.handle.net/10230/56039Understanding the molecular mechanisms that contribute to the appearance of chemotherapy resistant cell populations is necessary to improve cancer treatment. We have now investigated the role of β-catenin/CTNNB1 in the evolution of T-cell Acute Lymphoblastic Leukemia (T-ALL) patients and its involvement in therapy resistance. We have identified a specific gene signature that is directly regulated by β-catenin, TCF/LEF factors and ZBTB33/Kaiso in T-ALL cell lines, which is highly and significantly represented in five out of six refractory patients from a cohort of 40 children with T-ALL. By subsequent refinement of this gene signature, we found that a subset of β-catenin target genes involved with RNA-processing function are sufficient to segregate T-ALL refractory patients in three independent cohorts. We demonstrate the implication of β-catenin in RNA and protein synthesis in T-ALL and provide in vitro and in vivo experimental evidence that β-catenin is crucial for the cellular response to chemotherapy, mainly in the cellular recovery phase after treatment. We propose that combination treatments involving chemotherapy plus β-catenin inhibitors will enhance chemotherapy response and prevent disease relapse in T-ALL patients.application/pdfeng© 2023 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/articlehttp://dx.doi.org/10.15252/emmm.202216554KaisoRNA processingT-ALLChemotherapy resistanceβ-catenininfo:eu-repo/semantics/openAccess