AID expression is correlated with Bcr-Abl expression in CML-LBC and can be down-regulated by As2O3 and/or imatinib

Leuk Res. 2011 Oct;35(10):1355-9. doi: 10.1016/j.leukres.2011.04.020. Epub 2011 May 13.

Abstract

Activation-induced deaminase (AID), a cytidine deaminase, can accelerate the acquisition of BCR-ABL1 kinase domain mutations in human CML. In the present study, we investigated the expression of AID and Bcr-Abl in CML cells derived from 35 clinical patients. We found that both AID and Bcr-Abl were correlatively over-expressed in CML-LBC (lymphoid blast crisis) cells as compared with those in CML-CP (chronic phase) cells. AID expression was significantly decreased in CML-LBC cells after treated with arsenic trioxide, especially together with imatinib. We also observed satisfied therapy effects of As(2)O(3) and imatinib on patients with CML blast crisis. These data suggest that decreasing AID expression in CML-LBC by As(2)O(3) may be a promising approach to CML treatment.

MeSH terms

  • Adult
  • Antineoplastic Agents / pharmacology*
  • Arsenic Trioxide
  • Arsenicals / pharmacology
  • Benzamides
  • Blast Crisis / drug therapy*
  • Blast Crisis / genetics*
  • Blast Crisis / metabolism
  • Blast Crisis / pathology
  • Blotting, Western
  • Cells, Cultured
  • Cytidine Deaminase / genetics*
  • Cytidine Deaminase / metabolism
  • Down-Regulation / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Drug Synergism
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / metabolism
  • Gene Expression / drug effects
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Male
  • Middle Aged
  • Mutation
  • Oxides / pharmacology
  • Piperazines / pharmacology
  • Pyrimidines / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Benzamides
  • Oxides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase
  • Arsenic Trioxide