Abstract
We have identified differentially regulated genes in chronic myeloid leukemia (CML) cells upon short treatment with the broad-spectrum Bcr-Abl inhibitor dasatinib. The highly specific Bcr-Abl inhibitor nilotinib caused a very similar gene expression signature, validating the identified differentially regulated genes as a read-out of Bcr-Abl activity and implying that Bcr-Abl is the functionally central target of dasatinib in CML cells. Among the strongest downregulated genes, we have further validated the activation marker CD69 and the chemokine interleukin (IL)-8. Expression of both proteins is upregulated upon Bcr-Abl expression and inhibited by dasatinib and nilotinib. IL-8 may thus be a useful marker for the monitoring of CML inhibitor efficacy and play a potential pathophysiological role in CML.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / analysis*
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Antigens, CD / genetics
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Antigens, Differentiation, T-Lymphocyte / analysis*
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Antigens, Differentiation, T-Lymphocyte / genetics
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Biomarkers / analysis
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Dasatinib
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Down-Regulation / drug effects
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Drug Monitoring / methods*
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Fusion Proteins, bcr-abl / metabolism*
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Gene Expression Regulation, Neoplastic / drug effects
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Interleukin-8 / analysis*
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Interleukin-8 / genetics
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Lectins, C-Type
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
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Pyrimidines / pharmacology
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Thiazoles / pharmacology
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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Biomarkers
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CD69 antigen
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Interleukin-8
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Lectins, C-Type
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Pyrimidines
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Thiazoles
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Fusion Proteins, bcr-abl
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nilotinib
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Dasatinib