Mostrar el registro sencillo del ítem
dc.contributor.author | Martín Lorenzo, Alberto | |
dc.contributor.author | Auer, Franziska | |
dc.contributor.author | Chan, Lai N. | |
dc.contributor.author | García Ramírez, Idoia | |
dc.contributor.author | González-Herrero, Inés | |
dc.contributor.author | Rodríguez Hernández, Guillermo | |
dc.contributor.author | Bartenhagen, Christoph | |
dc.contributor.author | Dugas, Martin | |
dc.contributor.author | Gombert, Michael | |
dc.contributor.author | Ginzel, Sebastian | |
dc.contributor.author | Blanco Muñez, Óscar Javier | |
dc.contributor.author | Orfao de Matos Correia e Vale, José Alberto | |
dc.contributor.author | Alonso López, Diego | |
dc.contributor.author | Rivas Sanz, Javier de las | |
dc.contributor.author | García Cenador, María Begoña | |
dc.contributor.author | García Criado, Francisco Javier | |
dc.contributor.author | Müschen, Markus | |
dc.contributor.author | Sánchez García, Isidro | |
dc.contributor.author | Borkhardt, Arndt | |
dc.contributor.author | Vicente Dueñas, Carolina | |
dc.contributor.author | Hauer, Julia | |
dc.date.accessioned | 2024-02-06T09:13:06Z | |
dc.date.available | 2024-02-06T09:13:06Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Martín-Lorenzo, A., Auer, F., Chan, L. N., García-Ramírez, I., González-Herrero, I., Rodríguez-Hernández, G., Bartenhagen, C., Dugas, M., Gombert, M., Ginzel, S., Blanco, O., Orfao, A., Alonso-López, D., Rivas, J. D. L., García-Cenador, M. B., García-Criado, F. J., Müschen, M., Sánchez-García, I., Borkhardt, A., … Hauer, J. (2018). Loss of Pax5 Exploits Sca1-BCR-ABLp190 Susceptibility to Confer the Metabolic Shift Essential for pB-ALL. Cancer Research, 78(10), 2669-2679. https://doi.org/10.1158/0008-5472.CAN-17-3262 | es_ES |
dc.identifier.issn | 0008-5472 | |
dc.identifier.uri | http://hdl.handle.net/10366/155361 | |
dc.description.abstract | [EN]Preleukemic clones carrying BCR-ABL(P190) oncogenic lesions are found in neonatal cord blood, where the majority of preleukemic carriers do not convert into precursor B-cell acute lymphoblastic leukemia (pB-ALL). However, the critical question of how these preleukemic cells transform into pB-ALL remains undefined Here, we model a BCR-ABL(P190) preleukemic state and show that limiting BCR-ABL(P190) expression to hematopoietic stem/progenitor cells (HS/PC) in mice (Sca1-BCR-ABL(P190)) causes pB-ALL at low penetrance, which resembles the human disease. pB-ALL blast cells were BCR-ABL-negative and transcriptionally similar to pro-B/pre-B cells, suggesting disease onset upon reduced Pax5 functionality. Consistent with this, double Sca1-BCR- ABI(P190) +Pax5(+/-) mice developed pB-ALL with shorter latencies, 90% incidence, and accumulation of genomic alterations in the remaining wild-type Pax5 allele. Mechanistically, the Pax5-deficient leukemic pro-B cells exhibited a metabolic switch toward increased glucose utilization and energy metabolism. Transcriptome analysis revealed that metabolic genes (IDH1, G6PC3, GAPDH, PGK1, MYC, ENO1, ACO1) were upregulated in Pax5-deficient leukemic cells, and a similar metabolic signature could be observed in human leukemia. Our studies unveil the first in vivo evidence that the combination between Sca1-BCR-ABL(P190) and metabolic reprogramming imposed by reduced Pax5 expression is sufficient for pR-All. development. These findings might help to prevent conversion of BCR-ABL(P190) preleukemic cells. Significance: Loss of Pax5 drives metabolic reprogramming, which together with Scat-restricted BCR-ABL expression enables leukemic transformation. (C) 2018 AACR. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Association for Cancer Research | 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 | Gene-expression | es_ES |
dc.subject | BCR-ABL | es_ES |
dc.subject | Fusion genes | es_ES |
dc.subject | Stem-cells | es_ES |
dc.subject | Adult | es_ES |
dc.subject | Mice | es_ES |
dc.subject | Differentiation | es_ES |
dc.subject | Repression | es_ES |
dc.subject | Enrichment | es_ES |
dc.title | Loss of Pax5 exploits sca1-BCR-ABLp190 susceptibility to confer the metabolic shift essential for pB-ALL | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publishversion | https://doi.org/10.1158/0008-5472.CAN-21-3386 | es_ES |
dc.subject.unesco | 3201.01 Oncología | es_ES |
dc.identifier.doi | 10.1158/0008-5472.CAN-17-3262 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.essn | 1538-7445 | |
dc.journal.title | Cancer Research | es_ES |
dc.volume.number | 78 | es_ES |
dc.issue.number | 10 | es_ES |
dc.page.initial | 2669 | es_ES |
dc.page.final | 2679 | es_ES |
dc.type.hasVersion | info:eu-repo/semantics/acceptedVersion | es_ES |