Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-6-14
pubmed:abstractText
The resistance to the tyrosine kinase inhibitor imatinib in BCR/ABL-positive leukemias is mostly associated with mutations in the kinase domain of BCR/ABL, which include the most prevalent mutations E255K and T315I. Intriguingly, these mutations have also been identified in some patients before imatinib treatment. Here we examined the effects of these mutations on the kinase activity of a BCR/ABL kinase domain construct that also contained the SH3 and SH2 domains. When expressed in COS7 cells, the BCR/ABL construct with either E255K or T315I exhibited not only the resistance to imatinib but also the increase in activity to induce autophosphorylation as well as tyrosine phosphorylation of various cellular proteins, which included STAT5. The mutant kinases also showed increased activities in in vitro kinase assays. These results raise a possibility that the major imatinib resistance mutations E255K and T315I may confer the growth advantage on leukemic cells to expand in the absence of selective pressure from imatinib treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl, http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Piperazines, http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines, http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/Threonine, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/imatinib
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
319
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1272-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15194504-Animals, pubmed-meshheading:15194504-Antineoplastic Agents, pubmed-meshheading:15194504-COS Cells, pubmed-meshheading:15194504-Cercopithecus aethiops, pubmed-meshheading:15194504-DNA-Binding Proteins, pubmed-meshheading:15194504-Drug Resistance, Neoplasm, pubmed-meshheading:15194504-Enzyme Inhibitors, pubmed-meshheading:15194504-Fusion Proteins, bcr-abl, pubmed-meshheading:15194504-Glutamic Acid, pubmed-meshheading:15194504-Humans, pubmed-meshheading:15194504-Leukemia, pubmed-meshheading:15194504-Milk Proteins, pubmed-meshheading:15194504-Mutation, pubmed-meshheading:15194504-Phosphorylation, pubmed-meshheading:15194504-Piperazines, pubmed-meshheading:15194504-Protein Structure, Tertiary, pubmed-meshheading:15194504-Pyrimidines, pubmed-meshheading:15194504-STAT5 Transcription Factor, pubmed-meshheading:15194504-Threonine, pubmed-meshheading:15194504-Trans-Activators
pubmed:year
2004
pubmed:articleTitle
The two major imatinib resistance mutations E255K and T315I enhance the activity of BCR/ABL fusion kinase.
pubmed:affiliation
Department of Hematology and Oncology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't