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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 |
2003-5-2
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pubmed:abstractText |
Bcr-Abl is one of the most potent antiapoptotic molecules and is the tyrosine-kinase implicated in Philadelphia (Ph) chromosome-positive leukemia. It is still obscure how Bcr-Abl provides the leukemic cell a strong resistance to chemotherapeutic drugs. A rational drug development produced a specific inhibitor of the catalytic activity of Bcr-Abl called STI571. This drug was shown to eliminate Bcr-Abl-positive cells both in vitro and in vivo, although resistant cells may appear in culture and relapse occurs in some patients. In the study described here, Bcr-Abl-positive cells treated with tyrosine-kinase inhibitors such as herbimycin A, genistein or STI571 lost their phosphotyrosine-containing proteins, but were still extremely resistant to apoptosis. Therefore, in the absence of tyrosine-kinase activity, Bcr-Abl-positive cells continue to signal biochemically to prevent apoptosis induced by chemotherapeutic drugs. We propose that secondary antiapoptotic signals are entirely responsible for the resistance of Bcr-Abl-positive cells. Precise determination of such signals and rational drug development against them should improve the means to combat Ph chromosome-positive leukemia.
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pubmed:grant |
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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/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Genistein,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Quinones,
http://linkedlifedata.com/resource/pubmed/chemical/herbimycin,
http://linkedlifedata.com/resource/pubmed/chemical/imatinib
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1350-9047
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pubmed:author |
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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 |
592-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12728257-Antineoplastic Agents,
pubmed-meshheading:12728257-Apoptosis,
pubmed-meshheading:12728257-Benzoquinones,
pubmed-meshheading:12728257-Blotting, Western,
pubmed-meshheading:12728257-Caspases,
pubmed-meshheading:12728257-Drug Resistance, Neoplasm,
pubmed-meshheading:12728257-Fusion Proteins, bcr-abl,
pubmed-meshheading:12728257-Genistein,
pubmed-meshheading:12728257-HL-60 Cells,
pubmed-meshheading:12728257-Humans,
pubmed-meshheading:12728257-K562 Cells,
pubmed-meshheading:12728257-Lactams, Macrocyclic,
pubmed-meshheading:12728257-Piperazines,
pubmed-meshheading:12728257-Protein-Tyrosine Kinases,
pubmed-meshheading:12728257-Pyrimidines,
pubmed-meshheading:12728257-Quinones,
pubmed-meshheading:12728257-Time Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Bcr-Abl-mediated resistance to apoptosis is independent of constant tyrosine-kinase activity.
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pubmed:affiliation |
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Brazil.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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