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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2010-6-11
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pubmed:abstractText |
Despite initial remissions, most patients with Ph chromosome positive (Ph(+)) acute leukemia (AL) become refractory to tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib. This study was designed to determine if targeting the interleukin-3 receptor (IL-3R) with a diphtheria toxin fusion protein (DT(388)IL3) would improve the effectiveness of TKIs against Ph(+) AL cells. IL-3R subunits were detected on most Ph(+) cells and the IC50 for killing of colony forming cell (CFC) with DT(388)IL3 correlated with the level of IL-3Ralpha subunit by FACS. DT(388)IL3 synergized with both imatinib and dasatinib for killing of malignant CFCs. Long-term suspension culture-initiating cells (SC-ICs) and quiescent leukemic cells (G(0) in cell cycle) also were studied and synergistic interactions were again demonstrated. Thus, cotreatment with TKIs and DT(388)IL3 is much more effective in eliminating Ph(+) leukemic progenitors that express IL-3R than either agent alone.
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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/Diphtheria Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/IL3RA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3 Receptor alpha Subunit,
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/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/dasatinib,
http://linkedlifedata.com/resource/pubmed/chemical/diphtheria toxin-interleukin-3...,
http://linkedlifedata.com/resource/pubmed/chemical/imatinib
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1873-5835
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pubmed:author |
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pubmed:copyrightInfo |
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1035-42
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pubmed:meshHeading |
pubmed-meshheading:20137810-Adult,
pubmed-meshheading:20137810-Aged,
pubmed-meshheading:20137810-Blotting, Western,
pubmed-meshheading:20137810-Cell Cycle,
pubmed-meshheading:20137810-Cell Proliferation,
pubmed-meshheading:20137810-Cells, Cultured,
pubmed-meshheading:20137810-Diphtheria Toxin,
pubmed-meshheading:20137810-Drug Synergism,
pubmed-meshheading:20137810-Female,
pubmed-meshheading:20137810-Flow Cytometry,
pubmed-meshheading:20137810-Fusion Proteins, bcr-abl,
pubmed-meshheading:20137810-Humans,
pubmed-meshheading:20137810-Interleukin-3,
pubmed-meshheading:20137810-Interleukin-3 Receptor alpha Subunit,
pubmed-meshheading:20137810-Leukemia, Myeloid, Acute,
pubmed-meshheading:20137810-Male,
pubmed-meshheading:20137810-Middle Aged,
pubmed-meshheading:20137810-Neoplastic Stem Cells,
pubmed-meshheading:20137810-Piperazines,
pubmed-meshheading:20137810-Precursor Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:20137810-Protein-Tyrosine Kinases,
pubmed-meshheading:20137810-Pyrimidines,
pubmed-meshheading:20137810-RNA, Messenger,
pubmed-meshheading:20137810-Recombinant Fusion Proteins,
pubmed-meshheading:20137810-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20137810-Thiazoles
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pubmed:year |
2010
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pubmed:articleTitle |
A diphtheria toxin interleukin-3 fusion protein synergizes with tyrosine kinase inhibitors in killing leukemic progenitors from BCR/ABL positive acute leukemia.
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pubmed:affiliation |
Terry Fox Laboratory, British Columbia Cancer Agency and Department of Medicine, University of British Columbia, 675 West 10 Ave., Vancouver, BC, V5Z 1L3 Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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