Abstract
The Abl kinase inhibitor STI571 (imatinib mesylate) induces haematological remissions in many patients with chronic myeloid leukaemia (CML) but advanced stage CML usually becomes resistant to STI571. We describe a patient in whom progressive resistance to STI571 correlated with the appearance of a mutation in the Bcr-Abl kinase domain. This was a G to A transition that resulted in a glutamic acid to lysine substitution at position 255 (E255K) in the Abl type 1a protein. We suggest that the acquisition of point-mutations in the tyrosine kinase domain of Bcr-Abl may cause progressive clinical resistance to STI571.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Adult
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Amino Acid Substitution / genetics
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Antineoplastic Agents / therapeutic use*
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Benzamides
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Drug Resistance, Neoplasm / genetics
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / metabolism*
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Humans
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Imatinib Mesylate
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
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Male
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Piperazines / therapeutic use*
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Point Mutation / genetics*
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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Pyrimidines / therapeutic use*
Substances
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Antineoplastic Agents
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Benzamides
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Piperazines
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Pyrimidines
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Imatinib Mesylate
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Adenosine Triphosphate
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Protein-Tyrosine Kinases
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Fusion Proteins, bcr-abl