|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
4
|
|
pubmed:dateCreated |
2011-7-28
|
|
pubmed:abstractText |
The efficacy of tyrosine kinase (TK) inhibitors on non-cycling acute myeloid leukaemia (AML) cells, previously shown to have potent tumourigenic potential, is unknown. This pilot study describes the first attempt to characterize non-cycling cells from a small series of human FMS-like tyrosine kinase 3 (FLT3) mutation positive samples. CD34+ AML cells from patients with FLT3 mutation positive AML were cultured on murine stroma. In expansion cultures, non-cycling cells were found to retain CD34+ expression in contrast to dividing cells. Leukaemic gene rearrangements could be detected in non-cycling cells, indicating their leukaemic origin. Significantly, the FLT3-internal tandem duplication (ITD) mutation was found in the non-cycling fraction of four out of five cases. Exposure to the FLT3-directed inhibitor TKI258 clearly inhibited the growth of AML CD34+ cells in short-term cultures and colony-forming unit assays. Crucially, non-cycling cells were not eradicated, with the exception of one case, which exhibited exquisite sensitivity to the compound. Moreover, in longer-term cultures, TKI258-treated non-cycling cells showed no growth impairment compared to treatment-naive non-cycling cells. These findings suggest that non-cycling cells in AML may constitute a disease reservoir that is resistant to TK inhibition. Further studies with a larger sample size and other inhibitors are warranted.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
1365-2141
|
|
pubmed:author |
pubmed-author:AlvaresCaroline LCL,
pubmed-author:BartolovicKerolK,
pubmed-author:GonzalezDavidD,
pubmed-author:GreavesMelM,
pubmed-author:HulkkiSannaS,
pubmed-author:MorganGarethG,
pubmed-author:RoelLL,
pubmed-author:SchenkTinoT,
pubmed-author:SoChi W ECW,
pubmed-author:TitleyIanI,
pubmed-author:VijayaraghavanGowriG,
pubmed-author:YeungJennyJ
|
|
pubmed:copyrightInfo |
© 2011 Blackwell Publishing Ltd.
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
154
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
457-65
|
|
pubmed:meshHeading |
pubmed-meshheading:21689085-Adult,
pubmed-meshheading:21689085-Animals,
pubmed-meshheading:21689085-Antigens, CD34,
pubmed-meshheading:21689085-Antineoplastic Agents,
pubmed-meshheading:21689085-Benzimidazoles,
pubmed-meshheading:21689085-Cell Cycle,
pubmed-meshheading:21689085-Cell Survival,
pubmed-meshheading:21689085-Dose-Response Relationship, Drug,
pubmed-meshheading:21689085-Drug Evaluation, Preclinical,
pubmed-meshheading:21689085-Drug Resistance, Neoplasm,
pubmed-meshheading:21689085-Humans,
pubmed-meshheading:21689085-Leukemia, Myeloid, Acute,
pubmed-meshheading:21689085-Mice,
pubmed-meshheading:21689085-Middle Aged,
pubmed-meshheading:21689085-Mutation,
pubmed-meshheading:21689085-Pilot Projects,
pubmed-meshheading:21689085-Protein-Tyrosine Kinases,
pubmed-meshheading:21689085-Quinolones,
pubmed-meshheading:21689085-Tumor Cells, Cultured,
pubmed-meshheading:21689085-Tumor Stem Cell Assay,
pubmed-meshheading:21689085-Young Adult,
pubmed-meshheading:21689085-fms-Like Tyrosine Kinase 3
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Tyrosine kinase inhibitor insensitivity of non-cycling CD34+ human acute myeloid leukaemia cells with FMS-like tyrosine kinase 3 mutations.
|
|
pubmed:affiliation |
Section of Haemato-Oncology, The Institute of Cancer Research, Sutton, Surrey Department of Clinical Cytogenetics, The Royal Marsden Hospital, Sutton, Surrey. Caroline.Alvares@icr.ac.uk
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
