English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/24865
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

ERK2, but Not ERK1, Mediates Acquired and “De novo” Resistance to Imatinib Mesylate: Implication for CML Therapy

AuthorsAceves-Luquero, Clara I.; Esparís-Ogando, Azucena ; Pandiella, Atanasio
Issue Date1-Jul-2009
PublisherPublic Library of Science
CitationPLoS ONE 4(7): e6124 (2009)
AbstractResistance to Imatinib Mesylate (IM) is a major problem in Chronic Myelogenous Leukaemia management. Most of the studies about resistance have focused on point mutations on BCR/ABL. However, other types of resistance that do not imply mutations in BCR/ABL have been also described. In the present report we aim to study the role of several MAPK in IM resistance not associate to BCR/ABL mutations. Therefore we used an experimental system of resistant cell lines generated by co-culturing with IM (K562, Lama 84) as well as primary material from resistant and responder patient without BCR/ABL mutations. Here we demonstrate that Erk5 and p38MAPK signaling pathways are not implicated in the acquired resistance phenotype. However, Erk2, but not Erk1, is critical for the acquired resistance to IM. In fact, Bcr/Abl activates preferentially Erk2 in transient transfection in a dose dependent fashion through the c-Abl part of the chimeric protein. Finally, we present evidences demonstrating how constitutive activation of Erk2 is a de novo mechanism of resistance to IM. In summary our data support the use of therapeutic approaches based on Erk2 inhibition, which could be added to the therapeutic armamentarium to fight CML, especially when IM resistance develops secondary to Erk2 activation.
Description10 páginas, 6 figuras.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0006124
URIhttp://hdl.handle.net/10261/24865
DOI10.1371/journal.pone.0006124
ISSN1932-6203
Appears in Collections:(IBMCC) Artículos
Files in This Item:
File Description SizeFormat 
journal.pone.0006124.pdf720,36 kBAdobe 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.