Semi‑random mutagenesis profile of BCR‑ABL during imatinib resistance acquirement in K562 cells

Mol Med Rep. 2017 Dec;16(6):9409-9414. doi: 10.3892/mmr.2017.7835. Epub 2017 Oct 19.


Although imatinib is effective in chronic myeloid leukemia treatment, imatinib resistance due to the T315I mutation and/or other mutations is a challenge to be overcome. However, how DNA mutation occurs, particularly the T315I mutation, remains unclear. In the current study, the mutagenesis of BCR‑ABL was analyzed via focusing on the process of drug resistance, rather than the final results. Clone sequencing of the BCR‑ABL gene and other control genes was applied in two imatinib‑resistant cell models. The results have indicated that imatinib actively and selectively causes sporadic mutations in the BCR‑ABL gene, however not in the control genes. The majority of the mutations of BCR‑ABL were not the clinically observed T315I mutation, suggesting that the T315I mutation may be due to clonal expansion of cells with survival advantages. Taken together, the results of the current study elucidated the mutagenesis process during drug resistance and thus aids in the management of chemotherapy.

MeSH terms

  • Apoptosis / drug effects
  • Cell Proliferation / drug effects*
  • Drug Resistance, Neoplasm / genetics*
  • Fusion Proteins, bcr-abl / genetics*
  • Humans
  • Imatinib Mesylate / administration & dosage
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Mutagenesis / genetics
  • Mutation / genetics
  • Signal Transduction / drug effects


  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl