2026-09-15T21:33:40Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1551232025-04-30T19:28:43Zcom_10366_3974com_10366_3947com_10366_3946com_10366_3823col_10366_3975

García Ramírez, Idoia Bhatia, Sanil Rodríguez Hernández, Guillermo González-Herrero, Inés Walter, Carolin González de Tena‐Dávila, Sara Parvin, Salma Haas, Oskar Woessmann, Wilhelm Stanulla, Martin Schrappe, Martin Dugas, Martin Natkunam, Yasodha Orfao de Matos Correia e Vale, José Alberto Domínguez, Verónica Pintado, Belén Blanco, Óscar Alonso López, Diego Rivas Sanz, Javier de las Martín Lorenzo, Alberto Jiménez Fernández, Rafael García Criado, Francisco Javier García Cenador, María Begoña Lossos, Izidore S Vicente Dueñas, Carolina Borkhardt, Arndt Hauer, Julia Sánchez García, Isidro stem cells oncogenes mouse models epigenetic priming cancer initiation [EN]The impact of LMO2expression on cell lineage decisions duringT-cell leukemogenesis remains largely elusive. Using geneticlineage tracing, we have explored the potential of LMO2in dictat-ing a T-cell malignant phenotype. We first initiated LMO2expres-sion in hematopoietic stem/progenitor cells and maintained itsexpression in all hematopoietic cells. These mice develop exclu-sively aggressive human-like T-ALL. In order to uncover a potentialexclusive reprogramming effect of LMO2in murine hematopoieticstem/progenitor cells, we next showed that transient LMO2expression is sufficient for oncogenic function and induction ofT-ALL. The resulting T-ALLs lacked LMO2and its target-geneexpression, and histologically, transcriptionally, and geneticallysimilar to human LMO2-driven T-ALL. We next found that during T-ALL development, secondary genomic alterations take place withinthe thymus. However, the permissiveness for development of T-ALLseems to be associated with wider windows of differentiation thanpreviously appreciated. Restricted Cre-mediated activation ofLmo2at different stages of B-cell development induces systemati-cally and unexpectedly T-ALL that closely resembled those of theirnatural counterparts. Together, these results provide a novel para-digm for the generation of tumor T cells through reprogrammingin vivoand could be relevant to improve the response of T-ALL tocurrent therapies. 2024-01-31 2024-01-31 2018 info:eu-repo/semantics/article Garcia-Ramirez, I., Bhatia, S., Rodriguez-Hernandez, G., Gonzalez-Herrero, I., Walter, C., Gonzalez de Tena-Davila, S., Parvin, S., Haas, O., Woessmann, W., Stanulla, M., Schrappe, M., Dugas, M., Natkunam, Y., Orfao, A., Dominguez, V., Pintado, B., Blanco, O., Alonso-Lopez, D., De Las Rivas, J., … Sanchez-Garcia, I. (2018). Lmo2 expression defines tumor cell identity during T-cell leukemogenesis. EMBO JOURNAL, 37(14). https://doi.org/10.15252/embj.201798783 0261-4189 http://hdl.handle.net/10366/155123 10.15252/EMBJ.201798783 1460-2075 eng https://doi.org/10.15252/EMBJ.201798783 http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional Wiley