Abstract
Chronic myeloid leukaemia has a specific therapy: BCR/ABL inhibitor imatinib. Resistance due to BCR/ABL dependent and independent mechanisms is partially reversible by histone deacetylase inhibitors. We analysed by 2D-electrophoresis and anti-pan-acetylated and anti-phosphotyrosine immunoblots, followed by spot-matching and MALDI-TOF mass spectrometry, which proteome modifications would parallel restoration of sensitivity to imatinib by valproic acid (VPA). VPA plus imatinib significantly increased acetylation of HSP90 and hnRNP L and decreased phosphorylation of HSPs and hnRNPs in imatinib resistant cells. VPA was able to modify profoundly acetylome and phosphoproteome of CML cells, while reverting resistance to imatinib.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Apoptosis
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Benzamides
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Blotting, Western
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Cell Proliferation
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Drug Resistance, Neoplasm*
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Electrophoresis, Gel, Two-Dimensional
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / metabolism
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Histone Deacetylase Inhibitors / therapeutic use
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Humans
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Imatinib Mesylate
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Immunoprecipitation
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
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Phosphotyrosine / metabolism*
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Piperazines / adverse effects*
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Protein Kinase Inhibitors / adverse effects
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Proteome / analysis*
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Pyrimidines / adverse effects*
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RNA, Messenger / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Tumor Cells, Cultured
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Valproic Acid / therapeutic use*
Substances
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Benzamides
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Histone Deacetylase Inhibitors
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Piperazines
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Protein Kinase Inhibitors
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Proteome
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Pyrimidines
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RNA, Messenger
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Phosphotyrosine
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Valproic Acid
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Imatinib Mesylate
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Fusion Proteins, bcr-abl