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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2378-2381. Prepublished online as a Blood First Edition Paper on November 2, 2007; DOI 10.1182/blood-2007-06-096396. This Article Full Text (PDF) All Versions of this Article: blood-2007-06-096396v1 111/4/2378    most recent Alert me when this article is cited Alert me if a correction is posted 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 Khorashad, J. S. Articles by Kaeda, J. S Search for Related Content PubMed PubMed Citation Articles by Khorashad, J. S. Articles by Kaeda, J. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 18, 2007 Accepted October 28, 2007 In vivo kinetics of kinase domain mutations in CML patients treated with dasatinib after failing imatinib Jamshid S. Khorashad, Dragana Milojkovic, Puja Mehta, Mona Anand, Sara Ghorashian, Alistair G Reid, Valeria de Melo, Anna Babb, Hugues de Lavallade, Eduardo Olavarria, David Marin, John M Goldman*, Jane F Apperley, and Jaspal S Kaeda Department of Haematology, Imperial College London, London, United Kingdom * Corresponding author; email: j.goldman{at}imperial.ac.uk. We sought kinase domain (KD) mutations at the start of treatment with dasatinib in 46 CML patients resistant to or intolerant of imatinib. We identified BCR-ABL mutant subclones in 12 (26%) cases and used pyrosequencing to estimate subsequent changes in their relative size after starting dasatinib. Four patients lost their mutations which remained undetectable, three patients retained the original mutation or lost it only transiently, three lost their original mutations but acquired a new mutation (F317L) and two developed another mutation (T315I) in addition to the original mutation within the same subclone. This study shows that expansion of a mutant Ph-positive clone that responds initially to a second generation tyrosine kinase inhibitor may be due either to late acquisition of a second mutation in the originally mutated clone, such as the T315I, or to acquisition of a completely new mutant clone, such as F317L. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. P. Radich How I monitor residual disease in chronic myeloid leukemia Blood, October 15, 2009; 114(16): 3376 - 3381. [Abstract] [Full Text] [PDF] R. D. Press, S. G. Willis, J. Laudadio, M. J. Mauro, and M. W. N. Deininger Determining the rise in BCR-ABL RNA that optimally predicts a kinase domain mutation in patients with chronic myeloid leukemia on imatinib Blood, September 24, 2009; 114(13): 2598 - 2605. [Abstract] [Full Text] [PDF] S. Soverini, A. Gnani, S. Colarossi, F. Castagnetti, E. Abruzzese, S. Paolini, S. Merante, E. Orlandi, S. de Matteis, A. Gozzini, et al. Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors Blood, September 3, 2009; 114(10): 2168 - 2171. [Abstract] [Full Text] [PDF] E. Jabbour, J. E. Cortes, and H. M. Kantarjian Suboptimal Response to or Failure of Imatinib Treatment for Chronic Myeloid Leukemia: What Is the Optimal Strategy? Mayo Clin. Proc., February 1, 2009; 84(2): 161 - 169. [Abstract] [Full Text] [PDF] E. Jabbour, H. M. Kantarjian, D. Jones, N. Reddy, S. O'Brien, G. Garcia-Manero, J. Burger, and J. Cortes Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors Blood, December 15, 2008; 112(13): 4839 - 4842. [Abstract] [Full Text] [PDF]

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