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Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells
Authors: Albero, M.P. (M. Pilar)
Vaquer, J.M. (J.M.)
Andreu, E.J. (Enrique José)
Villanueva, J.J. (J.J.)
Franch, L. (L.)
Ivorra, C. (C.)
Poch, E. (Enric)
Aguirre, X. (Xavier)
Prosper, F. (Felipe)
Perez-Roger, I. (Ignacio)
Keywords: Bortezomib
CML
Bcr-Abl1
Imatinib resistance
Rb
Apoptosis
Issue Date: 2010
Publisher: Nature Publishing Group
Publisher version: http://dx.doi.org/10.1038/onc.2010.81
ISSN: 0950-9232
Citation: Albero, M.P., Vaquer, J.M., Andreu, E.J., Villanueva, J.J. et al. Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells. Oncogene 2010; 29: 3276–3286
Abstract
The use of c-abl-specific inhibitors such as Imatinib (IM) or Dasatinib has revolutionized the treatment of chronic myeloid leukemia (CML). However, a significant percentage of patients become resistant to IM. In this report, we have analyzed the possibility of using the proteasome as a molecular target in CML. Our results show that cells that express Bcr-Abl1 are more sensitive to the inhibition of the proteasome with Bortezomib (Btz) than control cells. This treatment reduces the proliferation of Bcr-Abl1- expressing cells, by inactivating NF-jB2 and decreasing the phosphorylation of Rb, eventually leading to an increase in caspase-dependent apoptosis. Furthermore, we show that Btz also induces cell-cycle arrest and apoptosis in cells expressing Bcr-Abl1 mutants that are resistant to IM. These results unravel a new molecular target of Btz, that is the Rb pathway, and open new possibilities in the treatment of CML especially for patients that become resistant to IM because of the presence of the T315I mutation.
Permanent link: http://hdl.handle.net/10171/18290
Appears in Collections:DA - CIMA - Oncología - Síndromes mieloproliferativos - Artículos de Revista
DA - CIMA - Oncología - Terapia celular - Artículos de Revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Hematología - Artículos de revista

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