Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib

DOI PDF 被引用文献11件
  • Amie S. Corbin
    From the Oregon Health and Science University Cancer Institute, Division of Hematology and Medical Oncology, Portland, OR; and III Medizinische Universitätsklinik, Fakultät für klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.
  • Paul La Rosée
    From the Oregon Health and Science University Cancer Institute, Division of Hematology and Medical Oncology, Portland, OR; and III Medizinische Universitätsklinik, Fakultät für klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.
  • Eric P. Stoffregen
    From the Oregon Health and Science University Cancer Institute, Division of Hematology and Medical Oncology, Portland, OR; and III Medizinische Universitätsklinik, Fakultät für klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.
  • Brian J. Druker
    From the Oregon Health and Science University Cancer Institute, Division of Hematology and Medical Oncology, Portland, OR; and III Medizinische Universitätsklinik, Fakultät für klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.
  • Michael W. Deininger
    From the Oregon Health and Science University Cancer Institute, Division of Hematology and Medical Oncology, Portland, OR; and III Medizinische Universitätsklinik, Fakultät für klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.

抄録

<jats:title>Abstract</jats:title> <jats:p>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 (Met244Val, Phe311Leu, Phe317Leu, Glu355Gly, Phe359Val, Val379Ile, Leu387Met, and His396Pro/Arg) 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 biologic characterization, before a resistant phenotype can be ascribed to a mutant.</jats:p>

収録刊行物

  • Blood

    Blood 101 (11), 4611-4614, 2003-06-01

    American Society of Hematology

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