Imatinib mesylate directly impairs class switch recombination through down-regulation of AID: its potential efficacy as an AID suppressor

Blood. 2012 Mar 29;119(13):3123-7. doi: 10.1182/blood-2011-01-327932. Epub 2012 Feb 14.


Activation-induced cytidine deaminase (AID) is essential for class switch recombination and somatic hypermutation. Its deregulated expression acts as a genomic mutator that can contribute to the development of various malignancies. During treatment with imatinib mesylate (IM), patients with chronic myeloid leukemia often develop hypogammaglobulinemia, the mechanism of which has not yet been clarified. Here, we provide evidence that class switch recombination on B-cell activation is apparently inhibited by IM through down-regulation of AID. Furthermore, expression of E2A, a key transcription factor for AID induction, was markedly suppressed by IM. These results elucidate not only the underlying mechanism of IM-induced hypogammaglobulinemia but also its potential efficacy as an AID suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides
  • Cytidine Deaminase / antagonists & inhibitors*
  • Cytidine Deaminase / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Drug Evaluation, Preclinical
  • Imatinib Mesylate
  • Immunoglobulin Class Switching / drug effects*
  • Immunosuppressive Agents / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use
  • Recombination, Genetic / drug effects
  • Recombination, Genetic / immunology
  • Sheep
  • Somatic Hypermutation, Immunoglobulin / drug effects
  • Treatment Outcome


  • Benzamides
  • Immunosuppressive Agents
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase