Imatinib resistance in CML

Cancer Lett. 2009 Feb 8;274(1):1-9. doi: 10.1016/j.canlet.2008.06.003. Epub 2008 Jul 23.


Imatinib is, at present, the first-choice treatment for patients with chronic myeloid leukaemia in chronic phase. Despite the impressive rate of complete haematological response and complete cytogenetical remissions, some cases show primary resistance or relapse after an initial response (secondary or acquired resistance). The most common mechanisms responsible for this resistance are BCR/ABL kinase domain mutations, BCR/ABL amplification and over-expression and clonal evolution with activation of additional oncogenic pathways. Here, we describe the molecular basis of imatinib resistance, the significance of molecular monitoring and the current efforts to overcome imatinib resistance, ranging from the development of new drugs to the stimulation of an immune response against the disease.

Publication types

  • Review

MeSH terms

  • Benzamides
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm / genetics*
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Piperazines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrimidines / therapeutic use*


  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl