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dc.contributor.author | Vicente Dueñas, Carolina | |
dc.contributor.author | Janssen, Stefan | |
dc.contributor.author | Oldenburg, Marina | |
dc.contributor.author | Auer, Franziska | |
dc.contributor.author | González‐Herrero, Inés | |
dc.contributor.author | Casado García, Ana | |
dc.contributor.author | Isidro Hernández, Marta | |
dc.contributor.author | Raboso Gallego, Javier | |
dc.contributor.author | Westhoff, Philipp | |
dc.contributor.author | Pandyra, Aleksandra A. | |
dc.contributor.author | Hein, Daniel | |
dc.contributor.author | Gössling, Katharina L. | |
dc.contributor.author | Alonso López, Diego | |
dc.contributor.author | de las Rivas, Javier | |
dc.contributor.author | Bhatia, Sanil | |
dc.contributor.author | García Criado, Francisco Javier | |
dc.contributor.author | García Cenador, María Begoña | |
dc.contributor.author | Weber, Andreas P. M. | |
dc.contributor.author | Köhrer, Karl | |
dc.contributor.author | Hauer, Julia | |
dc.contributor.author | Fischer, Ute | |
dc.contributor.author | Sánchez García, Isidro | |
dc.contributor.author | Borkhardt, Arndt | |
dc.date.accessioned | 2024-02-05T17:33:23Z | |
dc.date.available | 2024-02-05T17:33:23Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Vicente-Dueñas, C., Janssen, S., Oldenburg, M., Auer, F., González-Herrero, I., Casado-García, A., Isidro-Hernández, M., Raboso-Gallego, J., Westhoff, P., Pandyra, A. A., Hein, D., Gössling, K. L., Alonso-López, D., De Las Rivas, J., Bhatia, S., García-Criado, F. J., García-Cenador, M. B., Weber, A. P. M., Köhrer, K., … Borkhardt, A. (2020). An intact gut microbiome protects genetically predisposed mice against leukemia. Blood, 136(18), 2003-2017. https://doi.org/10.1182/blood.2019004381 | es_ES |
dc.identifier.issn | 0006-4971 | |
dc.identifier.uri | http://hdl.handle.net/10366/155352 | |
dc.description.abstract | [EN]The majority of childhood leukemias are precursor B-cell acute lymphoblastic leukemias (pB-ALLs) caused by a combination of prenatal genetic predispositions and oncogenic events occurring after birth. Although genetic predispositions are frequent in children (>1% to 5%), fewer than 1% of genetically predisposed carriers will develop pB-ALL. Although infectious stimuli are believed to play a major role in leukemogenesis, the critical determinants are not well defined. Here, by using murine models of pB-ALL, we show that microbiome disturbances incurred by antibiotic treatment early in life were sufficient to induce leukemia in genetically predisposed mice, even in the absence of infectious stimuli and independent of T cells. By using V4 and full-length 16S ribosomal RNA sequencing of a series of fecal samples, we found that genetic predisposition to pB-ALL (Pax5 heterozygosity or ETV6-RUNX1 fusion) shaped a distinct gut microbiome. Machine learning accurately (96.8%) predicted genetic predisposition using 40 of 3983 amplicon sequence variants as proxies for bacterial species. Transplantation of either wild-type (WT) or Pax51/- hematopoietic bone marrow cells into WT recipient mice revealed that the microbiome is shaped and determined in a donor genotype-specific manner. Gas chromatography-mass spectrometry (GC-MS) analyses of sera from WT and Pax51/- mice demonstrated the presence of a genotype-specific distinct metabolomic profile. Taken together, our data indicate that it is a lack of commensal microbiota rather than the presence of specific bacteria that promotes leukemia in genetically predisposed mice. Future large-scale longitudinal studies are required to determine whether targeted microbiome modification in children predisposed to pB-ALL could become a successful prevention strategy. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Society of Hematology | es_ES |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Acute Lymphoblastic-Leukemia | es_ES |
dc.subject | Childhood Leukemia | es_ES |
dc.subject | Gene-Expression | es_ES |
dc.subject | Cancer | es_ES |
dc.subject | Adult | es_ES |
dc.subject | Trends | es_ES |
dc.subject | Patterns | es_ES |
dc.subject | Risk | es_ES |
dc.subject.mesh | Disease Susceptibility | * |
dc.title | An intact gut microbiome protects genetically predisposed mice against leukemia | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publishversion | https://doi.org/10.1182/blood.2019004381 | es_ES |
dc.subject.unesco | 3201.01 Oncología | es_ES |
dc.identifier.doi | 10.1182/BLOOD.2019004381 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.essn | 1528-0020 | |
dc.journal.title | Blood | es_ES |
dc.volume.number | 136 | es_ES |
dc.issue.number | 18 | es_ES |
dc.page.initial | 2003 | es_ES |
dc.page.final | 2017 | es_ES |
dc.type.hasVersion | info:eu-repo/semantics/acceptedVersion | es_ES |
dc.subject.decs | susceptibilidad a enfermedades | * |