ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis

Leuk Res. 2003 Dec;27(12):1163-6. doi: 10.1016/s0145-2126(03)00117-6.

Abstract

Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. A point mutation leading to substitution at the ATP binding site of ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR-ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.

Publication types

  • Case Reports

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Benzamides
  • Blast Crisis / pathology*
  • Drug Resistance, Neoplasm / genetics*
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Imatinib Mesylate
  • Karyotyping
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Male
  • Molecular Sequence Data
  • Piperazines / therapeutic use*
  • Point Mutation / genetics*
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / metabolism
  • Pyrimidines / therapeutic use*
  • Sequence Homology, Nucleic Acid

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Adenosine Triphosphate
  • Fusion Proteins, bcr-abl
  • Proto-Oncogene Proteins c-abl