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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2128-2137. Prepublished online as a Blood First Edition Paper on May 24, 2005; DOI 10.1182/blood-2005-03-1036. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1036v1 106/6/2128    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Willis, S. G. Articles by Deininger, M. W. Search for Related Content PubMed PubMed Citation Articles by Willis, S. G. Articles by Deininger, M. W. Related Collections Neoplasia Oncogenes and Tumor Suppressors Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy Stephanie G. Willis, Thoralf Lange, Shadmehr Demehri, Sandra Otto, Lucy Crossman, Dietger Niederwieser, Eric P. Stoffregen, Shannon McWeeney, Ines Kovacs, Byung Park, Brian J. Druker, and Michael W. Deininger From the Oregon Health and Science University Cancer Institute, Portland, OR; the Department of Hematology, University of Leipzig, Leipzig, Germany; and the Howard Hughes Medical Institute. Mutations in the kinase domain (KD) of BCR-ABL are the leading cause of acquired imatinib resistance. In some cases, identical mutations were detected at relapse and in pretherapeutic specimens, consistent with selection of resistant clones in the presence of drug. However, the incidence of KD mutations in imatinibnaive patients, irrespective of response to therapy, is unknown. We studied mutation frequency in 66 patients with chronic myelogenous leukemia (CML), using cDNA sequencing and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) assays for 8 common mutations. Thirteen patients were positive by ASO-PCR only, 1 by ASO-PCR and sequencing, and 1 by sequencing only (overall frequency, 22.7%). T315I was most frequent (12% of patients). Eleven of the 14 patients with positive ASO-PCR had follow-up samples available for sequencing. Wild-type sequence was detected in 6 of 11, 2 different mutations in 1 of 11, and identical mutations in 4 of 11 patients, 2 of whom had achieved major cytogenetic response. In multivariate analysis mutation detection was associated with clonal cytogenetic evolution, exposure to 6-Thioguanine, and a low platelet count, but not with response to imatinib, event-free survival, and overall survival. KD mutants present at low levels do not invariably lead to relapse, and additional factors are required to induce a fully drug-resistant phenotype. (Blood. 2005; 106:2128-2137) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Mutation detection in CML: is it a useful tool? François Guilhot Blood 2005 106: 1897. [Full Text] [PDF] This article has been cited by other articles: T. Hughes, G. Saglio, S. Branford, S. Soverini, D.-W. Kim, M. C. Muller, G. Martinelli, J. Cortes, L. Beppu, E. Gottardi, et al. Impact of Baseline BCR-ABL Mutations on Response to Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase J. Clin. Oncol., September 1, 2009; 27(25): 4204 - 4210. 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