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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-12-3659. This Article Full Text (PDF) All Versions of this Article: 2002-12-3659v1 101/11/4611    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 Corbin, A. S Articles by Deininger, M. W Search for Related Content PubMed PubMed Citation Articles by Corbin, A. S Articles by Deininger, M. W Related Collections Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this? Submitted December 4, 2002 Accepted January 23, 2003 Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib Amie S Corbin, Paul La Rosee, Eric P Stoffregen, Brian J Druker, and Michael W Deininger* Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA Medizinische Universitatsklinik, Universitat Heidelberg, Mannheim, Germany * Corresponding author; email: deininge{at}ohsu.edu. Imatinib mesylate is a selective Bcr-Abl kinase inhibitor, effective in the treatment of chronic myelogenous leukemia. Most patients in chronic phase maintain durable responses, however, many in blast crisis fail to respond or relapse quickly. Kinase domain mutations are the most commonly identified mechanism associated with relapse. Many of these mutations decrease the sensitivity of the Abl kinase to imatinib, thus accounting for resistance to imatinib. The role of other mutations in the emergence of resistance has not been established. Using biochemical and cellular assays, we analyzed the sensitivity of several mutants (M244V, F311L, F317L, E355G, F359V, V379I, L387M and H396P/R) to imatinib mesylate to better understand their role in mediating resistance. While some Abl mutations lead to imatinib resistance, many others are significantly, and some fully, inhibited. This study highlights the need for biochemical and biological characterization, before a resistant phenotype can be ascribed to a mutant. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Resistance to imatinib mesylate in CML: all BCR-ABL mutations "are created equal but some are more equal than others" Junia V. Melo Blood 2003 101: 4231. 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