β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia
Abstract 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 it...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-01-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202216554 |
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| author | Violeta García‐Hernández David Arambilet Yolanda Guillén Teresa Lobo‐Jarne María Maqueda Christos Gekas Jessica González Arnau Iglesias Nerea Vega‐García Inés Sentís Juan L Trincado Ian Márquez‐López Holger Heyn Mireia Camós Lluis Espinosa Anna Bigas |
| author_facet | Violeta García‐Hernández David Arambilet Yolanda Guillén Teresa Lobo‐Jarne María Maqueda Christos Gekas Jessica González Arnau Iglesias Nerea Vega‐García Inés Sentís Juan L Trincado Ian Márquez‐López Holger Heyn Mireia Camós Lluis Espinosa Anna Bigas |
| author_sort | Violeta García‐Hernández |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-6d549c35fe4041b3aab8286bb2e7461c |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-6d549c35fe4041b3aab8286bb2e7461c2025-08-24T11:43:45ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-01-0115211710.15252/emmm.202216554β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemiaVioleta García‐Hernández0David Arambilet1Yolanda Guillén2Teresa Lobo‐Jarne3María Maqueda4Christos Gekas5Jessica González6Arnau Iglesias7Nerea Vega‐García8Inés Sentís9Juan L Trincado10Ian Márquez‐López11Holger Heyn12Mireia Camós13Lluis Espinosa14Anna Bigas15Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCProgram in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCProgram in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCProgram in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCProgram in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCProgram in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCProgram in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCProgram in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCHematology Laboratory, Hospital Sant Joan de Déu BarcelonaCNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)CNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCCNAG‐CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)Hematology Laboratory, Hospital Sant Joan de Déu BarcelonaProgram in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCProgram in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONCAbstract 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.https://doi.org/10.15252/emmm.202216554chemotherapy resistanceKaisoRNA processingT‐ALLβ‐catenin |
| spellingShingle | Violeta García‐Hernández David Arambilet Yolanda Guillén Teresa Lobo‐Jarne María Maqueda Christos Gekas Jessica González Arnau Iglesias Nerea Vega‐García Inés Sentís Juan L Trincado Ian Márquez‐López Holger Heyn Mireia Camós Lluis Espinosa Anna Bigas β‐Catenin activity induces an RNA biosynthesis program promoting therapy resistance in T‐cell acute lymphoblastic leukemia EMBO Molecular Medicine chemotherapy resistance Kaiso RNA processing T‐ALL β‐catenin |
| 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 | chemotherapy resistance Kaiso RNA processing T‐ALL β‐catenin |
| url | https://doi.org/10.15252/emmm.202216554 |
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