BCR-ABL1 kinase domain mutations may persist at very low levels for many years and lead to subsequent TKI resistance

Br J Cancer. 2013 Sep 17;109(6):1593-8. doi: 10.1038/bjc.2013.318. Epub 2013 Jun 25.

Abstract

Background: BCR-ABL1 mutation analysis is recommended for chronic myeloid leukaemia patients. However, mutations may become undetectable after changing therapy, and it is unknown whether they have been eradicated.

Methods: We examined longitudinal data of patients with imatinib-resistant mutations, which became undetectable by Sanger sequencing to determine whether mutations could reappear, and the related circumstances.

Results: Identical imatinib- and nilotinib-resistant mutations reappeared following further therapy changes in five patients, and was associated with subsequent nilotinib resistance in four.

Conclusion: The data suggest that some BCR-ABL1 mutations may persist at undetectable levels for many years after changing therapy, and can be reselected and confer resistance to subsequent inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzamides / pharmacology
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation*
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / pharmacology
  • Retrospective Studies

Substances

  • BCR-ABL1 fusion protein, human
  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • nilotinib