Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-8-23
pubmed:abstractText
Imatinib (imatinib mesylate, STI-571, Gleevec) is a selective BCR-ABL tyrosine kinase inhibitor that has been used as a highly effective chemoagent for treating chronic myelogenous leukemia. However, the initial response to imatinib is often followed by the recurrence of a resistant form of the disease, which is major obstacle to many therapeutic modalities. The aim of this study was to identify the gene expression signatures that confer resistance to imatinib. A series of four resistant K562 sublines was established with different imatinib dosage (200, 400, 600 and 800 nM) and analyzed using microarray technology. The transcripts of the genes showing universal or dose-dependent expression changes across the resistant sublines were identified. The gene sets associated with the imatinib-resistance were also identified using gene set enrichment analysis. In the resistant K562 sublines, the transcription- and apoptosis-related expression signatures were upregulated, whereas those related to the protein and energy metabolism were downregulated. Several genes identified in this study such as IGF1 and RAB11A have the potential to become surrogate markers useful in a clinical evaluation of imatinib-resistant patients without BCR-ABL mutation. The expression signatures identified in this study provide insights into the mechanism of imatinib-resistance and are expected to facilitate the development of an effective diagnostic and therapeutic strategy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1542-50
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Gene expression signatures associated with the resistance to imatinib.
pubmed:affiliation
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't