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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2004-9-28
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pubmed:abstractText |
Blast cell survival in suspension culture is associated with chemoresistance in acute myeloid leukaemia (AML). Autonomous production of IL-1beta by AML blasts is linked with a proliferative response, although its role in survival and hence apoptosis-resistance has not been examined in this disease. Cells that secreted more than 19.7 pg/ml IL-1beta were significantly more resistant to spontaneous apoptosis in 48-h culture than those that produced less than 19.7 pg/ml IL-1beta (P=0.008). Exogenous rhIL-1beta significantly enhanced 48-h survival in 25/29 blast cell samples (P=0.0001). IL-1 receptor ligation is known to activate at least three survival pathways: those mediated by PI-3 kinase, IL-1 receptor-associated kinase (IRAK) and ceramidase. In apoptosis-sensitive AML blasts with a strong survival response to rhIL-1beta, inhibitors of all three pathways down-modulated an IL-1beta-mediated increase in blast survival, but only the inhibition of all three pathways totally eliminated viable blasts. In apoptosis-resistant and apoptosis-sensitive primary AML samples, the three inhibitors all increased apoptosis in vitro after 48 h. Exogenous rhIL-1beta induced the hyperphosphorylation of Bcl-2. It also increased the activation of NF-kappaB in 5/15 blast samples. IL-1beta-mediated survival pathways may be a factor in apoptosis-resistance in primary AML blasts, and may therefore contribute to chemoresistance.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0887-6924
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1662-70
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15306822-Amidohydrolases,
pubmed-meshheading:15306822-Apoptosis,
pubmed-meshheading:15306822-Cell Division,
pubmed-meshheading:15306822-Ceramidases,
pubmed-meshheading:15306822-Enzyme Inhibitors,
pubmed-meshheading:15306822-Humans,
pubmed-meshheading:15306822-Interleukin-1,
pubmed-meshheading:15306822-Interleukin-1 Receptor-Associated Kinases,
pubmed-meshheading:15306822-Leukemia, Myeloid, Acute,
pubmed-meshheading:15306822-NF-kappa B,
pubmed-meshheading:15306822-Neoplastic Stem Cells,
pubmed-meshheading:15306822-Phenotype,
pubmed-meshheading:15306822-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15306822-Phosphorylation,
pubmed-meshheading:15306822-Protein Kinases,
pubmed-meshheading:15306822-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15306822-Recombinant Proteins,
pubmed-meshheading:15306822-Signal Transduction,
pubmed-meshheading:15306822-Tumor Cells, Cultured
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pubmed:year |
2004
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pubmed:articleTitle |
Interleukin-1beta maintains an apoptosis-resistant phenotype in the blast cells of acute myeloid leukaemia via multiple pathways.
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pubmed:affiliation |
Division of Haematology, University of Nottingham and Nottingham City Hospital, Nottingham, UK.
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pubmed:publicationType |
Journal Article
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