Abstract
The goal of this study was to ascertain the specific effects of 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG) treatment in human acute myelogenous leukemia (AML). Four human leukemia cell lines were treated with varying doses of 17-AAG followed by analysis of toxicity, apoptosis, proliferation, and cell cycle. Cell cycle analysis revealed that the cells accumulate in G2/M phase within 96 h of treatment, although the effect was not equivalent among the cell lines. p21, p53 expression and MDR1 activity were among the possible mechanisms uncovered for the differing responses. Exploiting these differences may allow for more effective combinatory treatments in patients with AML.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
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Apoptosis / drug effects
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Benzoquinones / pharmacology*
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Benzoquinones / therapeutic use
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Benzoquinones / toxicity
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Cell Cycle / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cyclin-Dependent Kinase Inhibitor p21
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G2 Phase / drug effects
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Humans
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Lactams, Macrocyclic / pharmacology*
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Lactams, Macrocyclic / therapeutic use
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Lactams, Macrocyclic / toxicity
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Leukemia, Myeloid, Acute / drug therapy*
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Tumor Suppressor Protein p53 / analysis
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Benzoquinones
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Lactams, Macrocyclic
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Tumor Suppressor Protein p53
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tanespimycin