Detection of early seeding of Richter transformation in chronic lymphocytic leukemia
Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with si...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/214988 |
| Acceso en línea: | https://hdl.handle.net/2445/214988 |
| Access Level: | acceso abierto |
| Palabra clave: | Leucèmia limfocítica crònica Limfomes Genètica Patologia Chronic lymphocytic leukemia Lymphomas Genetics Pathology |
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ES_25b7be00a07cbd41306b75c644c4c683 |
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oai:diposit.ub.edu:2445/214988 |
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ES |
| network_name_str |
España |
| spelling |
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia Nadeu Prat, Ferran Royo, Romina Massoni Badosa, Ramon Playà Albinyana, Heribert Garcia-Torre, Beatriz Duran Ferrer, Martí Dawson, Kevin J. Kulis, Marta Díaz Navarro, Ander Villamor i Casas, Neus Melero, Juan L. Chapaprieta, Vicente Dueso Barroso, Ana Delgado, Julio Moia, Riccardo Ruiz Gil, Sara Marchese, Domenica Giró, Ariadna Verdaguer Dot, Núria Clot Razquin, Guillem Rozman, María Frigola, Gerard Rivas Delgado, Alfredo Baumann, Tycho Alcoceba, Miguel González,Marco Climent, Fina Abrisqueta Costa, Pau Castellví, Josep Bosch, Francesc Aymerich Gregorio, Marta Enjuanes, Anna Ruiz Gaspà, Silvia López Guillermo, Armando Jares Gerboles, Pedro Beà Bobet, Sílvia M. Capella Gutiérrez, Salvador Jesús, 1985- Gelpí Buchaca, Josep Lluís López Bigas, Núria Torrents Arenales, David Campbell, Peter J. Gut, Ivo G. Rossi, Davide Gaidano, Gianluca Puente, Xose S. Garcia Roves, Pablo M. Colomer Pujol, Dolors Heyn, Holger Maura, Francesco Martín-Subero, José Ignacio Campo Güerri, Elias Leucèmia limfocítica crònica Limfomes Genètica Patologia Chronic lymphocytic leukemia Lymphomas Genetics Pathology Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)high-B cell receptor (BCR)low-signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT. Nature Publishing Group https://hdl.handle.net/2445/214988 |
| title |
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia |
| spellingShingle |
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia Nadeu Prat, Ferran Leucèmia limfocítica crònica Limfomes Genètica Patologia Chronic lymphocytic leukemia Lymphomas Genetics Pathology |
| title_short |
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia |
| title_full |
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia |
| title_fullStr |
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia |
| title_full_unstemmed |
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia |
| title_sort |
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia |
| author |
Nadeu Prat, Ferran |
| author_facet |
Nadeu Prat, Ferran Royo, Romina Massoni Badosa, Ramon Playà Albinyana, Heribert Garcia-Torre, Beatriz Duran Ferrer, Martí Dawson, Kevin J. Kulis, Marta Díaz Navarro, Ander Villamor i Casas, Neus Melero, Juan L. Chapaprieta, Vicente Dueso Barroso, Ana Delgado, Julio Moia, Riccardo Ruiz Gil, Sara Marchese, Domenica Giró, Ariadna Verdaguer Dot, Núria Clot Razquin, Guillem Rozman, María Frigola, Gerard Rivas Delgado, Alfredo Baumann, Tycho Alcoceba, Miguel González,Marco Climent, Fina Abrisqueta Costa, Pau Castellví, Josep Bosch, Francesc Aymerich Gregorio, Marta Enjuanes, Anna Ruiz Gaspà, Silvia López Guillermo, Armando Jares Gerboles, Pedro Beà Bobet, Sílvia M. Capella Gutiérrez, Salvador Jesús, 1985- Gelpí Buchaca, Josep Lluís López Bigas, Núria Torrents Arenales, David Campbell, Peter J. Gut, Ivo G. Rossi, Davide Gaidano, Gianluca Puente, Xose S. Garcia Roves, Pablo M. Colomer Pujol, Dolors Heyn, Holger Maura, Francesco Martín-Subero, José Ignacio Campo Güerri, Elias |
| author_role |
author |
| author2 |
Royo, Romina Massoni Badosa, Ramon Playà Albinyana, Heribert Garcia-Torre, Beatriz Duran Ferrer, Martí Dawson, Kevin J. Kulis, Marta Díaz Navarro, Ander Villamor i Casas, Neus Melero, Juan L. Chapaprieta, Vicente Dueso Barroso, Ana Delgado, Julio Moia, Riccardo Ruiz Gil, Sara Marchese, Domenica Giró, Ariadna Verdaguer Dot, Núria Clot Razquin, Guillem Rozman, María Frigola, Gerard Rivas Delgado, Alfredo Baumann, Tycho Alcoceba, Miguel González,Marco Climent, Fina Abrisqueta Costa, Pau Castellví, Josep Bosch, Francesc Aymerich Gregorio, Marta Enjuanes, Anna Ruiz Gaspà, Silvia López Guillermo, Armando Jares Gerboles, Pedro Beà Bobet, Sílvia M. Capella Gutiérrez, Salvador Jesús, 1985- Gelpí Buchaca, Josep Lluís López Bigas, Núria Torrents Arenales, David Campbell, Peter J. Gut, Ivo G. Rossi, Davide Gaidano, Gianluca Puente, Xose S. Garcia Roves, Pablo M. Colomer Pujol, Dolors Heyn, Holger Maura, Francesco Martín-Subero, José Ignacio Campo Güerri, Elias |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| topic |
Leucèmia limfocítica crònica Limfomes Genètica Patologia Chronic lymphocytic leukemia Lymphomas Genetics Pathology |
| topic_facet |
Leucèmia limfocítica crònica Limfomes Genètica Patologia Chronic lymphocytic leukemia Lymphomas Genetics Pathology |
| description |
Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)high-B cell receptor (BCR)low-signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT. |
| publishDate |
2022 |
| format |
article |
| status_str |
publishedVersion |
| url |
https://hdl.handle.net/2445/214988 |
| eu_rights_str_mv |
openAccess |
| publisher |
Nature Publishing Group |
| institution |
Universidad de Barcelona |
| collection |
Dipòsit Digital de la UB |
| reponame_str |
Dipòsit Digital de la UB |
| instname_str |
Universidad de Barcelona |
| _version_ |
1878432567472947200 |
| publishDateSort |
2022 |
| author_browse |
Abrisqueta Costa, Pau Alcoceba, Miguel Aymerich Gregorio, Marta Baumann, Tycho Beà Bobet, Sílvia M. Bosch, Francesc Campbell, Peter J. Campo Güerri, Elias Capella Gutiérrez, Salvador Jesús, 1985- Castellví, Josep Chapaprieta, Vicente Climent, Fina Clot Razquin, Guillem Colomer Pujol, Dolors Dawson, Kevin J. Delgado, Julio Dueso Barroso, Ana Duran Ferrer, Martí Díaz Navarro, Ander Enjuanes, Anna Frigola, Gerard Gaidano, Gianluca Garcia Roves, Pablo M. Garcia-Torre, Beatriz Gelpí Buchaca, Josep Lluís Giró, Ariadna González,Marco Gut, Ivo G. Heyn, Holger Jares Gerboles, Pedro Kulis, Marta López Bigas, Núria López Guillermo, Armando Marchese, Domenica Martín-Subero, José Ignacio Massoni Badosa, Ramon Maura, Francesco Melero, Juan L. Moia, Riccardo Nadeu Prat, Ferran Playà Albinyana, Heribert Puente, Xose S. Rivas Delgado, Alfredo Rossi, Davide Royo, Romina Rozman, María Ruiz Gaspà, Silvia Ruiz Gil, Sara Torrents Arenales, David Verdaguer Dot, Núria Villamor i Casas, Neus |
| publisherStr |
Nature Publishing Group |
| score |
6,9303427 |