Your browser doesn't support javascript.
loading
Lmo2 expression defines tumor cell identity during T-cell leukemogenesis.
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, Alberto; Domínguez, Verónica; Pintado, Belén; Blanco, Oscar; Alonso-López, Diego; De Las Rivas, Javier; Martín-Lorenzo, Alberto; Jiménez, Rafael; García Criado, Francisco Javier; García Cenador, María Begoña; Lossos, Izidore S; Vicente-Dueñas, Carolina; Borkhardt, Arndt; Hauer, Julia; Sánchez-García, Isidro.
Afiliación
  • García-Ramírez I; Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Salamanca, Spain.
  • Bhatia S; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
  • Rodríguez-Hernández G; Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine University Dusseldorf, Dusseldorf, Germany.
  • González-Herrero I; Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Salamanca, Spain.
  • Walter C; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
  • González de Tena-Dávila S; Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Salamanca, Spain.
  • Parvin S; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
  • Haas O; Institute of Medical Informatics, University of Muenster, Muenster, Germany.
  • Woessmann W; Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Salamanca, Spain.
  • Stanulla M; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
  • Schrappe M; Division of Hematology-Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
  • Dugas M; Department of Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
  • Natkunam Y; Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria.
  • Orfao A; Department of Pediatric Hematology and Oncology, Justus-Liebig-University Giessen, Giessen, Germany.
  • Domínguez V; Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
  • Pintado B; Department of Pediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
  • Blanco O; Institute of Medical Informatics, University of Muenster, Muenster, Germany.
  • Alonso-López D; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • De Las Rivas J; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
  • Martín-Lorenzo A; Servicio de Citometría and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
  • Jiménez R; Transgenesis Facility CNB-CBMSO, CSIC-UAM, Madrid, Spain.
  • García Criado FJ; Transgenesis Facility CNB-CBMSO, CSIC-UAM, Madrid, Spain.
  • García Cenador MB; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
  • Lossos IS; Departamento de Anatomía Patológica, Universidad de Salamanca, Salamanca, Spain.
  • Vicente-Dueñas C; Bioinformatics Unit, Cancer Research Center (CSIC-USAL), Salamanca, Spain.
  • Borkhardt A; Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
  • Hauer J; Bioinformatics and Functional Genomics Research Group, Cancer Research Center (CSIC-USAL), Salamanca, Spain.
  • Sánchez-García I; Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Salamanca, Spain.
EMBO J ; 37(14)2018 07 13.
Article en En | MEDLINE | ID: mdl-29880602
The impact of LMO2 expression on cell lineage decisions during T-cell leukemogenesis remains largely elusive. Using genetic lineage tracing, we have explored the potential of LMO2 in dictating a T-cell malignant phenotype. We first initiated LMO2 expression in hematopoietic stem/progenitor cells and maintained its expression in all hematopoietic cells. These mice develop exclusively aggressive human-like T-ALL In order to uncover a potential exclusive reprogramming effect of LMO2 in murine hematopoietic stem/progenitor cells, we next showed that transient LMO2 expression is sufficient for oncogenic function and induction of T-ALL The resulting T-ALLs lacked LMO2 and its target-gene expression, and histologically, transcriptionally, and genetically similar to human LMO2-driven T-ALL We next found that during T-ALL development, secondary genomic alterations take place within the thymus. However, the permissiveness for development of T-ALL seems to be associated with wider windows of differentiation than previously appreciated. Restricted Cre-mediated activation of Lmo2 at different stages of B-cell development induces systematically and unexpectedly T-ALL that closely resembled those of their natural counterparts. Together, these results provide a novel paradigm for the generation of tumor T cells through reprogramming in vivo and could be relevant to improve the response of T-ALL to current therapies.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transformación Celular Neoplásica / Proteínas Adaptadoras Transductoras de Señales / Leucemia-Linfoma Linfoblástico de Células T Precursoras / Proteínas con Dominio LIM / Carcinogénesis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: EMBO J Año: 2018 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transformación Celular Neoplásica / Proteínas Adaptadoras Transductoras de Señales / Leucemia-Linfoma Linfoblástico de Células T Precursoras / Proteínas con Dominio LIM / Carcinogénesis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: EMBO J Año: 2018 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido