Abstract
It would be of great value to predict the efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of individual CML patients. We propose an immunoblot system for detecting the phosphorylation of Crkl, a major target of Bcr-Abl, in blood samples after in vitro incubation with TKIs. When the remaining phosphorylated Crkl after treatment with imatinib was evaluated as the "residual index (RI)", high values were found in accordance with imatinib resistance. Moreover, RI reflected the outcome of imatinib- as well as second generation TKIs with a high sensitivity and specificity. Therefore, this system should be useful in the selection of TKIs.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Adult
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Aged
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Aged, 80 and over
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Biomarkers, Pharmacological / analysis
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Biomarkers, Pharmacological / metabolism
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Biomarkers, Tumor / analysis
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Biomarkers, Tumor / metabolism
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Cells, Cultured
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Female
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Fusion Proteins, bcr-abl / metabolism*
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Humans
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K562 Cells
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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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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
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Male
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Middle Aged
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Nuclear Proteins / metabolism
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Phosphorylation
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Predictive Value of Tests
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Prognosis
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Protein Kinases / analysis
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Protein Kinases / metabolism*
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Sensitivity and Specificity
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Treatment Outcome
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Young Adult
Substances
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Adaptor Proteins, Signal Transducing
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Biomarkers, Pharmacological
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Biomarkers, Tumor
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CRKL protein
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Nuclear Proteins
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Protein Kinase Inhibitors
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Protein Kinases
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Fusion Proteins, bcr-abl