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

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...

Descripción completa

Detalles Bibliográficos
Autores:	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
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

id	ES_25b7be00a07cbd41306b75c644c4c683
oai_identifier_str	oai:diposit.ub.edu:2445/214988
network_acronym_str	ES
network_name_str	España
repository_id_str
spelling	Detection of early seeding of Richter transformation in chronic lymphocytic leukemiaNadeu Prat, FerranRoyo, RominaMassoni Badosa, RamonPlayà Albinyana, HeribertGarcia-Torre, BeatrizDuran Ferrer, MartíDawson, Kevin J.Kulis, MartaDíaz Navarro, AnderVillamor i Casas, NeusMelero, Juan L.Chapaprieta, VicenteDueso Barroso, AnaDelgado, JulioMoia, RiccardoRuiz Gil, SaraMarchese, DomenicaGiró, AriadnaVerdaguer Dot, NúriaClot Razquin, GuillemRozman, MaríaFrigola, GerardRivas Delgado, AlfredoBaumann, TychoAlcoceba, MiguelGonzález,MarcoCliment, FinaAbrisqueta Costa, PauCastellví, JosepBosch, FrancescAymerich Gregorio, MartaEnjuanes, AnnaRuiz Gaspà, SilviaLópez Guillermo, ArmandoJares Gerboles, PedroBeà Bobet, Sílvia M.Capella Gutiérrez, Salvador Jesús, 1985-Gelpí Buchaca, Josep LluísLópez Bigas, NúriaTorrents Arenales, DavidCampbell, Peter J.Gut, Ivo G.Rossi, DavideGaidano, GianlucaPuente, Xose S.Garcia Roves, Pablo M.Colomer Pujol, DolorsHeyn, HolgerMaura, FrancescoMartín-Subero, José IgnacioCampo Güerri, EliasLeucèmia limfocítica crònicaLimfomesGenèticaPatologiaChronic lymphocytic leukemiaLymphomasGeneticsPathologyRichter 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 Group2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/214988Articles publicats en revistes (Fonaments Clínics)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41591-022-01927-8Nature Medicine, 2022, vol. 28, num.8, p. 1662-1671https://doi.org/10.1038/s41591-022-01927-8cc-by(c) Nadeu, Ferran et al., 2022http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2149882026-05-27T06:46:51Z
dc.title.none.fl_str_mv	Detection of early seeding of Richter transformation in chronic lymphocytic leukemia
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
dc.creator.none.fl_str_mv	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	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
dc.subject.none.fl_str_mv	Leucèmia limfocítica crònica Limfomes Genètica Patologia Chronic lymphocytic leukemia Lymphomas Genetics Pathology
topic	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
dc.date.none.fl_str_mv	2022
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/214988
url	https://hdl.handle.net/2445/214988
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1038/s41591-022-01927-8 Nature Medicine, 2022, vol. 28, num.8, p. 1662-1671 https://doi.org/10.1038/s41591-022-01927-8
dc.rights.none.fl_str_mv	cc-by(c) Nadeu, Ferran et al., 2022 http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by(c) Nadeu, Ferran et al., 2022 http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Nature Publishing Group
publisher.none.fl_str_mv	Nature Publishing Group
dc.source.none.fl_str_mv	Articles publicats en revistes (Fonaments Clínics) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona
instname_str	Universidad de Barcelona
reponame_str	Dipòsit Digital de la UB
collection	Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869404778876895232
score	15,81155

Detection of early seeding of Richter transformation in chronic lymphocytic leukemia

Similares en LA Referencia