β-Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T-cell acute lymphoblastic leukemia.

Autor: García-Hernández V; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., Arambilet D; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., Guillén Y; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., Lobo-Jarne T; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., Maqueda M; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., Gekas C; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., González J; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., Iglesias A; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., Vega-García N; Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain.; Developmental Tumor Biology Group, Leukemia and Other Pediatric Hemopathies, Institut de Recerca Sant Joan de Déu, CIBERER, Barcelona, Spain., Sentís I; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Trincado JL; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Márquez-López I; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., Heyn H; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain., Camós M; Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain.; Developmental Tumor Biology Group, Leukemia and Other Pediatric Hemopathies, Institut de Recerca Sant Joan de Déu, CIBERER, Barcelona, Spain., Espinosa L; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain., Bigas A; Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, Barcelona, Spain.; Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2023 Feb 08; Vol. 15 (2), pp. e16554. Date of Electronic Publication: 2023 Jan 04.
DOI: 10.15252/emmm.202216554
Abstrakt: Understanding 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.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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