The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug Resistance in Chronic Myeloid Leukemia Academic Article uri icon


MeSH Major

  • B-Lymphocytes
  • Blast Crisis
  • Cytidine Deaminase
  • Drug Resistance, Neoplasm
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Mutation
  • Piperazines
  • Pyrimidines


  • Chronic myeloid leukemia (CML) is induced by BCR-ABL1 and can be effectively treated for many years with Imatinib until leukemia cells acquire drug resistance through BCR-ABL1 mutations and progress into fatal B lymphoid blast crisis (LBC). Despite its clinical significance, the mechanism of progression into LBC is unknown. Here, we show that LBC but not CML cells express the B cell-specific mutator enzyme AID. We demonstrate that AID expression in CML cells promotes overall genetic instability by hypermutation of tumor suppressor and DNA repair genes. Importantly, our data uncover a causative role of AID activity in the acquisition of BCR-ABL1 mutations leading to Imatinib resistance, thus providing a rationale for the rapid development of drug resistance and blast crisis progression.

publication date

  • September 8, 2009



  • Academic Article



  • eng

PubMed Central ID

  • PMC2931825

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2009.07.030

PubMed ID

  • 19732723

Additional Document Info

start page

  • 232

end page

  • 45


  • 16


  • 3