Abstract
Using MTT, Annexin V/flow cytometry, immunocytochemistry, subcellular fractionation, and Western blotting assays we analyzed the effect of imatinib in two blast phase of chronic myeloid leukemia (CML) cell lines: K562 P-glycoprotein (Pgp)-negative, and Lucena, Pgp-positive. In K562 cell line, the high apoptosis index induced by imatinib was associated with the survivin predominantly in the nucleus. In the Lucena cell line, the low apoptosis index induced by imatinib was associated with a cytoplasmatic survivin localization. Pgp and survivin might be subject to the same molecular regulation, and therefore represent a therapeutic target in the blast phase of CML.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Annexin A5 / metabolism
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Apoptosis / genetics
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Benzamides
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Blast Crisis / drug therapy
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Blast Crisis / genetics
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Blast Crisis / pathology*
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Blotting, Western
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Cell Nucleus / metabolism
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Cell Nucleus / pathology
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Cell Survival / drug effects
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Cytoplasm / metabolism
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Cytoplasm / pathology
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Flow Cytometry
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Gene Expression Regulation, Neoplastic
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Humans
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Imatinib Mesylate
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Immunohistochemistry
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Inhibitor of Apoptosis Proteins / genetics*
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Inhibitor of Apoptosis Proteins / metabolism
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K562 Cells
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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 / pathology
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Piperazines / pharmacology*
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Pyrimidines / pharmacology*
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Survivin
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Annexin A5
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Antineoplastic Agents
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BIRC5 protein, human
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Benzamides
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Inhibitor of Apoptosis Proteins
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Piperazines
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Pyrimidines
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Survivin
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Imatinib Mesylate