| http://purl.uniprot.org/citations/20007699 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20007699 | http://www.w3.org/2000/01/rdf-schema#comment | "Acquired resistance through genetic mutations is a common phenomenon in several cancer therapies using molecularly targeted drugs, best exemplified by the BCR-ABL inhibitor imatinib in treating chronic myelogenous leukemia (CML). Overcoming acquired resistance is a daunting therapeutic challenge, and little is known about how these mutations evolve. To facilitate understanding the resistance mechanisms, we developed a novel culture model for CML acquired resistance in which the CML cell line KCL-22, following initial response to imatinib, develops resistant T315I BCR-ABL mutation. We demonstrate that the emergence of BCR-ABL mutations do not require pre-existing BCR-ABL mutations derived from the original patient as the subclones of KCL-22 cells can form various BCR-ABL mutations upon imatinib treatment. BCR-ABL mutation rates vary from cell clone to clone and passages, in contrast to the relatively stable mutation rate of the hypoxanthine-guanine phosphoribosyltransferase gene. Strikingly, development of BCR-ABL mutations depends on its gene expression because BCR-ABL knockdown completely blocks KCL-22 cell relapse on imatinib and acquisition of mutations. We further show that the endogenous BCR-ABL locus has significantly higher mutagenesis potential than the transduced randomly integrated BCR-ABL cDNA. Our study suggests important roles of BCR-ABL gene expression and its native chromosomal locus for acquisition of BCR-ABL mutations and provides a new tool for further studying resistance mechanisms."xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.039206"xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/author | "Chen W."xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/author | "Gao C."xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/author | "Huang Q."xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/author | "Wang Z."xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/author | "Yuan H."xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/author | "Bhatia R."xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/author | "Chen W.'"xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/author | "Yee J.K."xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/pages | "5085-5096"xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/title | "BCR-ABL gene expression is required for its mutations in a novel KCL-22 cell culture model for acquired resistance of chronic myelogenous leukemia."xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://purl.uniprot.org/core/volume | "285"xsd:string |
| http://purl.uniprot.org/citations/20007699 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20007699 |
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