dc.contributor.author | Isidro-Hernández, Marta | |
dc.contributor.author | Casado-García, Ana | |
dc.contributor.author | Oak, Ninad | |
dc.contributor.author | Alemán-Arteaga, Silvia | |
dc.contributor.author | Ruiz-Corzo, Belén | |
dc.contributor.author | Martínez-Cano, Jorge | |
dc.contributor.author | Mayado, Andrea | |
dc.contributor.author | Sánchez, Elena G | |
dc.contributor.author | Blanco, Oscar | |
dc.contributor.author | Gaspar, Maria Luisa | |
dc.contributor.author | Orfao, Alberto | |
dc.contributor.author | Alonso-López, Diego | |
dc.contributor.author | De Las Rivas, Javier | |
dc.contributor.author | Riesco, Susana | |
dc.contributor.author | Prieto-Matos, Pablo | |
dc.contributor.author | González-Murillo, África | |
dc.contributor.author | García-Criado, Francisco Javier | |
dc.contributor.author | García-Cenador, María Begoña | |
dc.contributor.author | Ramírez-Orellana, Manuel | |
dc.contributor.author | Andres, Belen de | |
dc.contributor.author | Vicente-Dueñas, Carolina | |
dc.contributor.author | Cobaleda, César | |
dc.contributor.author | Nichols, Kim E | |
dc.contributor.author | Sánchez-García, Isidro | |
dc.date.accessioned | 2023-12-18T20:38:11Z | |
dc.date.available | 2023-12-18T20:38:11Z | |
dc.date.issued | 2023-08-24 | |
dc.identifier.citation | Nat Commun. 2023 Aug 24;14(1):5159. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/16839 | |
dc.description.abstract | The initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children. Several preclinical studies have shown that exposure to immune stressors triggers the transformation of preleukemic B cells to full-blown B-ALL, but how this takes place is still a longstanding and unsolved challenge. Here we show that dysregulation of innate immunity plays a driving role in the clonal evolution of pre-malignant Pax5+/- B-cell precursors toward leukemia. Transcriptional profiling reveals that Myd88 is downregulated in immune-stressed pre-malignant B-cell precursors and in leukemic cells. Genetic reduction of Myd88 expression leads to a significant increase in leukemia incidence in Pax5+/-Myd88+/- mice through an inflammation-dependent mechanism. Early induction of Myd88-independent Toll-like receptor 3 signaling results in a significant delay of leukemia development in Pax5+/- mice. Altogether, these findings identify a role for innate immunity dysregulation in leukemia, with important implications for understanding and therapeutic targeting of the preleukemic state in children. | es_ES |
dc.description.sponsorship | Research at C. Cobaleda’s laboratory was partially supported by Ministerio de Ciencia e Innovación/AEI/FEDER (PID2021-122787OB-I00), and a Research Contract with the “Fundación Síndrome de Wolf-Hirschhorno 4p-”. Institutional grants from the “Fundación Ramón Areces” and “Banco de Santander” to the CBMSO are also acknowledged. Research in C. Vicente-Dueñas group has been funded by Instituto de Salud Carlos III through the project “ PI22/00379 and by a “Miguel Servet Grant” [CPII19/00024-AES 2017-2020; co-funded by European Regional Development Fund (ERDF)/European Social Fund (ESF) “A way to make Europe”/“Investing in your future”]. Kim Nichols receives funding from the American Lebanese Syrian Associated Charities (ALSAC) and R01CA241452 from the National Cancer institute Research in ISG group is partially supported by FEDER and by SAF2015-64420-R MINECO/FEDER, UE; by RTI2018-093314-B-I00 MCIU/AEI/FEDER, UE; by PID2021-122185OB-I00 MCIU/AEI/FEDER, UE, and by Junta de Castilla y León (UIC-017, CSI001U16, CSI234P18, and CSI144P20). Research in BdA group is partially supported by RTI2019-09114-B-I00 MCIU/AEI/FEDER, UE. M. Ramírez-Orellana and I. Sánchez-García have been supported by the Fundacion Unoentrecienmil (CUNINA project). C. Cobaleda, M. Ramírez-Orellana, and I. Sánchez-García have been supported by the Fundación Científica de la Asociación Española contra el Cáncer (PRYCO211305SANC). A. Casado-García (CSI067-18) and M. Isidro-Hernández (CSI021-19) are supported by FSE-Conserjería de Educación de la Junta de Castilla y León 2019 and 2020 (ESF, European Social Fund) fellowship, respectively. S. Alemán-Arteaga is supported by an Ayuda para Contratos predoctorales para la formación de doctores (PRE2019-088887). J. Martínez-Cano is supported by a predoctoral fellowship FPI-UAM 2019. We also thank the Hartwell Center and Dr. Ti-Cheng Chang from the Center for Bioinformatics at SJCRH for their support of the whole genome sequencing and bioinformatic pipelines. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Burkitt Lymphoma | es_ES |
dc.subject.mesh | Leukemia | es_ES |
dc.subject.mesh | Precursor B-Cell Lymphoblastic Leukemia-Lymphoma | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Precursor Cells, B-Lymphoid | es_ES |
dc.subject.mesh | Myeloid Differentiation Factor 88 | es_ES |
dc.subject.mesh | Signal Transduction | es_ES |
dc.subject.mesh | Adaptor Proteins, Signal Transducing | es_ES |
dc.subject.mesh | Immunity, Innate | es_ES |
dc.title | Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice | es_ES |
dc.type | research article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 37620322 | es_ES |
dc.format.volume | 14 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 5159 | es_ES |
dc.identifier.doi | 10.1038/s41467-023-40961-z | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Agencia Estatal de Investigación (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Fundación Ramón Areces | es_ES |
dc.contributor.funder | Banco Santander | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | American Lebanese Syrian Associated Charities | es_ES |
dc.contributor.funder | National Cancer Research Institute | es_ES |
dc.contributor.funder | Junta de Castilla y León (España) | es_ES |
dc.contributor.funder | Fundación Unoentrecienmil | es_ES |
dc.contributor.funder | Asociación Española Contra el Cáncer | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41467-023-40961-z | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2021-122787OB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/MINECO//SAF2015-64420-R/ES/MECANISMOS MOLECULARES RESPONSABLES DE LA REPROGRAMACION TUMORAL DE PROGENITORES HEMATOPOYETICOS MEDIADA POR BCL6/ | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RTI2018-093314-B-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2021-122185OB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RTI2019-09114-B-I00 | es_ES |
dc.relation.projectFIS | info:fis/Instituto de Salud Carlos III///PI22- Proyectos de I+D+I en salud (AES 2022). (2022)/PI22/00379 | es_ES |
dc.relation.projectFIS | info:fis/Instituto de Salud Carlos III/Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I/null/Contratos Miguel Servet tipo II (2019)/CPII19/00024 | es_ES |