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

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 involve...

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Autores principales: García‐Hernández, Violeta, Arambilet, David, Guillén, Yolanda, Lobo‐Jarne, Teresa, Maqueda, María, Gekas, Christos, González, Jessica, Iglesias, Arnau, Vega‐García, Nerea, Sentís, Inés, Trincado, Juan L, Márquez‐López, Ian, Heyn, Holger, Camós, Mireia, Espinosa, Lluis, Bigas, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9906382/
https://www.ncbi.nlm.nih.gov/pubmed/36597789
http://dx.doi.org/10.15252/emmm.202216554
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author García‐Hernández, Violeta
Arambilet, David
Guillén, Yolanda
Lobo‐Jarne, Teresa
Maqueda, María
Gekas, Christos
González, Jessica
Iglesias, Arnau
Vega‐García, Nerea
Sentís, Inés
Trincado, Juan L
Márquez‐López, Ian
Heyn, Holger
Camós, Mireia
Espinosa, Lluis
Bigas, Anna
author_facet García‐Hernández, Violeta
Arambilet, David
Guillén, Yolanda
Lobo‐Jarne, Teresa
Maqueda, María
Gekas, Christos
González, Jessica
Iglesias, Arnau
Vega‐García, Nerea
Sentís, Inés
Trincado, Juan L
Márquez‐López, Ian
Heyn, Holger
Camós, Mireia
Espinosa, Lluis
Bigas, Anna
author_sort García‐Hernández, Violeta
collection PubMed
description 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.
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spelling pubmed-99063822023-02-13 β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia García‐Hernández, Violeta Arambilet, David Guillén, Yolanda Lobo‐Jarne, Teresa Maqueda, María Gekas, Christos González, Jessica Iglesias, Arnau Vega‐García, Nerea Sentís, Inés Trincado, Juan L Márquez‐López, Ian Heyn, Holger Camós, Mireia Espinosa, Lluis Bigas, Anna EMBO Mol Med Articles 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. John Wiley and Sons Inc. 2023-01-04 /pmc/articles/PMC9906382/ /pubmed/36597789 http://dx.doi.org/10.15252/emmm.202216554 Text en © 2023 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
García‐Hernández, Violeta
Arambilet, David
Guillén, Yolanda
Lobo‐Jarne, Teresa
Maqueda, María
Gekas, Christos
González, Jessica
Iglesias, Arnau
Vega‐García, Nerea
Sentís, Inés
Trincado, Juan L
Márquez‐López, Ian
Heyn, Holger
Camós, Mireia
Espinosa, Lluis
Bigas, Anna
β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia
title β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia
title_full β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia
title_fullStr β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia
title_full_unstemmed β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia
title_short β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia
title_sort β‐catenin activity induces an rna biosynthesis program promoting therapy resistance in t‐cell acute lymphoblastic leukemia
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9906382/
https://www.ncbi.nlm.nih.gov/pubmed/36597789
http://dx.doi.org/10.15252/emmm.202216554
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