rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2001-3-26
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pubmed:abstractText |
This study demonstrates in both stable and inducible BCR-ABL-expressing hematopoietic cells a down-regulation of the major mammalian DNA repair protein DNA-PKcs by BCR-ABL. Similar results were found in BCR-ABL CD34(+) cells from patients with chronic myelogenous leukemia (CML). DNA-PKcs down-regulation is a proteasome-dependent degradation that requires tyrosine kinase activity and is associated with a marked DNA repair deficiency along with increased sensitivity to ionizing radiation. The conjunction of a major DNA repair deficiency and a resistance to apoptosis, both induced by BCR-ABL, provides a new mechanism to explain how secondary genetic alterations can accumulate in CML, eventually leading to blast crisis. The down-regulation of DNA-PKcs was reversible in CD34(+) CML cells suggesting that this approach might offer a novel and powerful therapeutic strategy in this disease, especially to delay the blast crisis. (Blood. 2001;97:2084-2090)
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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 |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Activated Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/PRKDC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/lactacystin,
http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin AG957
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:AbdulKarimBB,
pubmed-author:BourhisJJ,
pubmed-author:DeutschEE,
pubmed-author:DugrayAA,
pubmed-author:EschwegeFF,
pubmed-author:M'KacherRR,
pubmed-author:MaggiorellaLL,
pubmed-author:MarangoniEE,
pubmed-author:RoweG BGB,
pubmed-author:TurhanA GAG,
pubmed-author:VaganaySS,
pubmed-author:VainchenkerWW
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2084-90
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11264175-Acetylcysteine,
pubmed-meshheading:11264175-Animals,
pubmed-meshheading:11264175-Apoptosis,
pubmed-meshheading:11264175-Blast Crisis,
pubmed-meshheading:11264175-Child,
pubmed-meshheading:11264175-Cysteine Endopeptidases,
pubmed-meshheading:11264175-DNA, Neoplasm,
pubmed-meshheading:11264175-DNA Repair,
pubmed-meshheading:11264175-DNA-Activated Protein Kinase,
pubmed-meshheading:11264175-DNA-Binding Proteins,
pubmed-meshheading:11264175-Enzyme Induction,
pubmed-meshheading:11264175-Enzyme Inhibitors,
pubmed-meshheading:11264175-Fusion Proteins, bcr-abl,
pubmed-meshheading:11264175-Gene Expression Regulation, Leukemic,
pubmed-meshheading:11264175-Humans,
pubmed-meshheading:11264175-In Situ Hybridization, Fluorescence,
pubmed-meshheading:11264175-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:11264175-Mice,
pubmed-meshheading:11264175-Multienzyme Complexes,
pubmed-meshheading:11264175-Neuroblastoma,
pubmed-meshheading:11264175-Nuclear Proteins,
pubmed-meshheading:11264175-Oligopeptides,
pubmed-meshheading:11264175-Precursor B-Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:11264175-Protease Inhibitors,
pubmed-meshheading:11264175-Proteasome Endopeptidase Complex,
pubmed-meshheading:11264175-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11264175-Recombinant Fusion Proteins,
pubmed-meshheading:11264175-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11264175-Transfection,
pubmed-meshheading:11264175-Tumor Cells, Cultured,
pubmed-meshheading:11264175-Tumor Stem Cell Assay,
pubmed-meshheading:11264175-Tyrphostins
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pubmed:year |
2001
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pubmed:articleTitle |
BCR-ABL down-regulates the DNA repair protein DNA-PKcs.
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pubmed:affiliation |
UPRES EA 27-10 Radiosensibilité-Radiocarcinogenèse Humaine and METSI, Institut Gustave Roussy, Villejuif, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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