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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0023467,
umls-concept:C0038250,
umls-concept:C0205225,
umls-concept:C0683598,
umls-concept:C1318444,
umls-concept:C1333568,
umls-concept:C1515654,
umls-concept:C1704788
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pubmed:issue |
7
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pubmed:dateCreated |
2008-7-16
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pubmed:abstractText |
Relapse in acute myeloid leukaemia (AML) is mediated by survival of leukaemic stem cells following remission-induction chemotherapy. It would therefore be useful to identify therapeutic agents that target leukaemic stem cells. We devised a flow cytometric chemosensitivity assay allowing 48 h culture of leukaemic blasts in a defined microenvironment followed by enumeration of viable CD34+CD38-CD123+ leukaemic stem and progenitor cells (LSPC). The assay was used to investigate the LSPC response to cytosine arabinoside (Ara-C) and to the FLT3 inhibitor AG1296. There was a 3.6-fold increase in Ara-C-treated LSPC survival under defined 'niche-like' conditions compared to culture without microenvironmental support. Nine AML samples with internal tandem duplications of FLT3 (FLT3/ITDs) were treated with AG1296. Three samples were very sensitive (>50% kill) and 4 were moderately sensitive (10-50% kill) in bulk suspension culture without microenvironmental support. However, under defined 'niche-like' conditions, the survival of LSPC was enhanced rather than inhibited by AG1296 treatment. We conclude that an interaction between LSPC and a defined in vitro microenvironment models a chemoresistant niche. Our data point to a need to investigate more novel chemotherapeutic agents under these stringent conditions to identify agents that may be suitable to target minimal residual disease in AML.
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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/6,7-dimethoxy-3-phenylquinoxaline,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD38,
http://linkedlifedata.com/resource/pubmed/chemical/CD38 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytarabine,
http://linkedlifedata.com/resource/pubmed/chemical/FLT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IL3RA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3 Receptor alpha Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-3,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/fms-Like Tyrosine Kinase 3
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1476-5551
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1395-401
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18509353-Antigens, CD34,
pubmed-meshheading:18509353-Antigens, CD38,
pubmed-meshheading:18509353-Cell Line, Tumor,
pubmed-meshheading:18509353-Cell Survival,
pubmed-meshheading:18509353-Cytarabine,
pubmed-meshheading:18509353-Drug Resistance, Neoplasm,
pubmed-meshheading:18509353-Humans,
pubmed-meshheading:18509353-Interleukin-3 Receptor alpha Subunit,
pubmed-meshheading:18509353-Leukemia, Myeloid, Acute,
pubmed-meshheading:18509353-Membrane Glycoproteins,
pubmed-meshheading:18509353-Neoplastic Stem Cells,
pubmed-meshheading:18509353-Phenotype,
pubmed-meshheading:18509353-Receptors, Interleukin-3,
pubmed-meshheading:18509353-Tyrphostins,
pubmed-meshheading:18509353-fms-Like Tyrosine Kinase 3
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pubmed:year |
2008
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pubmed:articleTitle |
Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment.
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pubmed:affiliation |
Division of Haematology, University of Nottingham, Nottingham, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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