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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2006-11-13
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pubmed:abstractText |
BCL-2 proteins are critical for cell survival and are overexpressed in many tumors. ABT-737 is a small-molecule BH3 mimetic that exhibits single-agent activity against lymphoma and small-cell lung cancer in preclinical studies. We here report that ABT-737 effectively kills acute myeloid leukemia blast, progenitor, and stem cells without affecting normal hematopoietic cells. ABT-737 induced the disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway. In cells with phosphorylated BCL-2 or increased MCL-1, ABT-737 was inactive. Inhibition of BCL-2 phosphorylation and reduction of MCL-1 expression restored sensitivity to ABT-737. These data suggest that ABT-737 could be a highly effective antileukemia agent when the mechanisms of resistance identified here are considered.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABT-737,
http://linkedlifedata.com/resource/pubmed/chemical/Biphenyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrophenols,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2 Homologous Antagonist-Killer...,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/myeloid cell leukemia sequence 1...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1535-6108
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pubmed:author |
pubmed-author:AndreeffMichaelM,
pubmed-author:ContractorRoohaR,
pubmed-author:DengXingmingX,
pubmed-author:DietrichMartinM,
pubmed-author:EstrovZeevZ,
pubmed-author:HarrisDavidD,
pubmed-author:JiffarTilahunT,
pubmed-author:KitadaShinichiS,
pubmed-author:KonoplevaMarinaM,
pubmed-author:LingXiaoyangX,
pubmed-author:MariniFrank CFC,
pubmed-author:MayW StratfordWS,
pubmed-author:McCubreyJamesJ,
pubmed-author:McQueenTeresaT,
pubmed-author:ObaM SMS,
pubmed-author:ReedJohn CJC,
pubmed-author:RuvoloPeter PPP,
pubmed-author:RuvoloVivian RVR,
pubmed-author:SamudioIsmaelI,
pubmed-author:SchoberWendy DWD,
pubmed-author:ShiYue-XiYX,
pubmed-author:SneedThomasT,
pubmed-author:SoengasMariaM,
pubmed-author:VerhaegenMoniqueM,
pubmed-author:WattJulie CJC,
pubmed-author:ZhaiDayongD
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
375-88
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pubmed:dateRevised |
2008-7-9
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pubmed:meshHeading |
pubmed-meshheading:17097560-Animals,
pubmed-meshheading:17097560-Apoptosis,
pubmed-meshheading:17097560-Biphenyl Compounds,
pubmed-meshheading:17097560-Cell Line,
pubmed-meshheading:17097560-Dimerization,
pubmed-meshheading:17097560-Drug Resistance, Neoplasm,
pubmed-meshheading:17097560-Hematopoietic Stem Cells,
pubmed-meshheading:17097560-Humans,
pubmed-meshheading:17097560-Leukemia, Myeloid, Acute,
pubmed-meshheading:17097560-Mice,
pubmed-meshheading:17097560-Neoplasm Proteins,
pubmed-meshheading:17097560-Nitrophenols,
pubmed-meshheading:17097560-Piperazines,
pubmed-meshheading:17097560-Protein Conformation,
pubmed-meshheading:17097560-Protein Structure, Tertiary,
pubmed-meshheading:17097560-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:17097560-RNA, Small Interfering,
pubmed-meshheading:17097560-Recombinant Fusion Proteins,
pubmed-meshheading:17097560-Sulfonamides,
pubmed-meshheading:17097560-bcl-2 Homologous Antagonist-Killer Protein,
pubmed-meshheading:17097560-bcl-2-Associated X Protein
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pubmed:year |
2006
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pubmed:articleTitle |
Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia.
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pubmed:affiliation |
Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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