Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2001-3-26
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)
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
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
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2084-90
pubmed:dateRevised
2009-11-19
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
pubmed:year
2001
pubmed:articleTitle
BCR-ABL down-regulates the DNA repair protein DNA-PKcs.
pubmed:affiliation
UPRES EA 27-10 Radiosensibilité-Radiocarcinogenèse Humaine and METSI, Institut Gustave Roussy, Villejuif, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't