دورية أكاديمية
Lmo2 expression defines tumor cell identity during T‐cell leukemogenesis
| العنوان: | Lmo2 expression defines tumor cell identity during T‐cell leukemogenesis |
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| المؤلفون: | 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, 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 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2018 |
| المجموعة: | Universidad de Salamanca: Gredos (Gestión del Repositorio Documental de la Universidad de Salamanca) |
| مصطلحات موضوعية: | stem cells, oncogenes, mouse models, epigenetic priming, cancer initiation, Disease Models, Animal, Cell Transformation, Neoplastic, Adaptor Proteins, Signal Transducing, Carcinogenesis, 3201.01 Oncología, proteínas adaptadoras transductoras de señales, modelos de enfermedad en animales, carcinogénesis, transformación celular neoplásica |
| الوصف: | [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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0261-4189 1460-2075 |
| العلاقة: | https://doi.org/10.15252/EMBJ.201798783Test; 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.201798783Test; http://hdl.handle.net/10366/155123Test |
| DOI: | 10.15252/EMBJ.201798783 |
| الإتاحة: | https://doi.org/10.15252/EMBJ.201798783Test https://doi.org/10.15252/embj.201798783Test http://hdl.handle.net/10366/155123Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 Internacional ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; info:eu-repo/semantics/embargoedAccess |
| رقم الانضمام: | edsbas.17E0C9BE |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 02614189 14602075 |
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| DOI: | 10.15252/EMBJ.201798783 |