English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/182401
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

The NOTCH1/CD44 axis drives pathogenesis in a T cell acute lymphoblastic leukemia model

AuthorsGarcía-Peydró, Marina ; Fuentes, Patricia ; Mosquera, Marta ; García-León, María J. ; Alcaín, Juan ; Toribio, María Luisa
Issue Date7-Jul-2018
CitationJOURNAL OF CLINICAL INVESTIGATION 128: 2802- 2818 (2018)
AbstractNOTCH1 is a prevalent signaling pathway in T cell acute lymphoblastic leukemia (T-ALL), but crucial NOTCH1 downstream signals and target genes contributing to T-ALL pathogenesis cannot be retrospectively analyzed in patients and thus remain ill defined. This information is clinically relevant, as initiating lesions that lead to cell transformation and leukemia-initiating cell (LIC) activity are promising therapeutic targets against the major hurdle of T-ALL relapse. Here, we describe the generation in vivo of a human T cell leukemia that recapitulates T-ALL in patients, which arises de novo in immunodeficient mice reconstituted with human hematopoietic progenitors ectopically expressing active NOTCH1. This T-ALL model allowed us to identify CD44 as a direct NOTCH1 transcriptional target and to recognize CD44 overexpression as an early hallmark of preleukemic cells that engraft the BM and finally develop a clonal transplantable T-ALL that infiltrates lymphoid organs and brain. Notably, CD44 is shown to support crucial BM niche interactions necessary for LIC activity of human T-ALL xenografts and disease progression, highlighting the importance of the NOTCH1/CD44 axis in T-ALL pathogenesis. The observed therapeutic benefit of anti-CD44 antibody administration in xenotransplanted mice holds great promise for therapeutic purposes against T-ALL relapse.
URIhttp://hdl.handle.net/10261/182401
Identifiersdoi: 10.1172/JCI92981
issn: 1558-8238
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
ToribioML_TheNOTCH1-CD44.pdf5,77 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.