Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/62213
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Type: Journal article
Title: Gaining insights into the Bcr-Abl activity-independent mechanisms of resistance to imatinib mesylate in KCL22 cells: A comparative proteomic approach
Author: Colavita, I.
Esposito, N.
Martinelli, R.
Catanzano, F.
Vaz de Melo, J.
Pane, F.
Ruoppolo, M.
Salvatore, F.
Citation: BBA: Proteins and Proteomics, 2010; 1804(10):1974-1987
Publisher: Elsevier Science BV
Issue Date: 2010
ISSN: 1570-9639
1878-1454
Statement of
Responsibility: 
Irene Colavita, Nicola Esposito, Rosanna Martinelli, Francesca Catanzano, Junia V. Melo, Fabrizio Pane, Margherita Ruoppolo, Francesco Salvatore
Abstract: Imatinib mesylate is a potent inhibitor of Bcr-Abl tyrosine kinase, an oncoprotein that plays a key role in the development of chronic myeloid leukemia. Consequently, imatinib is used as front-line therapy for this disease. A major concern in imatinib treatment is the emergence of resistance to the drug. Here we used the imatinib-resistant KCL22R and imatinib-sensitive KCL22S cells in which none of the known resistance mechanisms has been detected and hence novel Bcr-Abl activity-independent mechanisms could be envisaged. We characterized proteins that were differentially expressed between the KCL22R and KCL22S cells. Using two-dimensional differential gel electrophoresis coupled with mass spectrometry and Western blot analysis we identified 51 differentially expressed proteins: 27 were over-expressed and 24 were under-expressed in KCL22R versus KCL22S cells. Several of these proteins are likely to be involved in such survival mechanisms as modulation of redox balance and activation of anti-apoptotic pathways mediated by NF-kappaB and Ras-MAPK signaling. The data reported may be useful for further studies on mechanisms of imatinib resistance and for the screening of biomarkers to develop new combinatorial therapeutic approaches.
Keywords: Bcr-Abl
2D differential gel electrophoresis
Chronic myeloid leukemia
Imatinib resistance
KCL22 cell
Rights: Copyright © 2010 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.bbapap.2010.04.009
Published version: http://dx.doi.org/10.1016/j.bbapap.2010.04.009
Appears in Collections:Animal and Veterinary Sciences publications
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