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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2242-2249. Prepublished online as a Blood First Edition Paper on May 11, 2007; DOI 10.1182/blood-2007-03-066936. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-03-066936v1 110/7/2242    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 O'Hare, T. Articles by Deininger, M. W. N. Search for Related Content PubMed PubMed Citation Articles by O'Hare, T. Articles by Deininger, M. W. N. Related Collections Perspectives Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PERSPECTIVE Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia Thomas O'Hare1,2, Christopher A. Eide2, and Michael W. N. Deininger2 1 Howard Hughes Medical Institute, Chevy Chase, MD; 2 Oregon Health & Science University Cancer Institute, Portland, OR Mutations in the kinase domain (KD) of BCR-ABL are the most prevalent mechanism of acquired imatinib resistance in patients with chronic myeloid leukemia (CML). Here we examine predisposing factors underlying acquisition of KD mutations, evidence for acquisition of mutations before and during therapy, and whether the detection of a KD mutation universally implies resistance. We also provide a perspective on how the second-line Abl inhibitors dasatinib and nilotinib are faring in the treatment of imatinib-resistant CML, especially in relation to specific KD mutations. We discuss the growing importance of the multi-inhibitor–resistant 315T>I mutant and the therapeutic potential that a 315T>I inhibitor would have. Last, we assess the potential of Abl kinase inhibitor combinations to induce stable responses even in advanced CML and interpret the emerging data in the context of CML pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Brehme, O. Hantschel, J. Colinge, I. Kaupe, M. Planyavsky, T. Kocher, K. Mechtler, K. L. Bennett, and G. Superti-Furga Charting the molecular network of the drug target Bcr-Abl PNAS, May 5, 2009; 106(18): 7414 - 7419. [Abstract] [Full Text] [PDF] F. Castagnetti, F. Palandri, M. Amabile, N. Testoni, S. Luatti, S. Soverini, I. 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