Therapeutic application of small interfering RNA directed against bcr-abl transcripts to a patient with imatinib-resistant chronic myeloid leukaemia

Clin Exp Med. 2007 Jun;7(2):47-55. doi: 10.1007/s10238-007-0125-z. Epub 2007 Jul 4.


RNA interference is referred to as the recently discovered process of sequence-specific, post-transcriptional gene silencing that is initiated by double-stranded RNA molecules known as small interfering RNAs (siRNA). We herein present a first report on the in vivo application of targeted non-virally delivered synthetic bcr-abl siRNA in a female patient with recurrent Philadelphia chromosome-positive chronic myeloid leukaemia (CML) resistant to imatinib (Y253F mutation) and chemotherapy after allogeneic haematopoietic stem cell transplantation. We found a remarkable inhibition of the overexpressed bcr-abl oncogene resulting in increased apoptosis of CML cells. In vivo siRNA application was well tolerated without any clinically adverse events. Our findings imply that the clinical application of synthetic siRNA is feasible, safe and has real potential for genetic-based therapies using synthetic non-viral carriers.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides
  • Blood Cell Count
  • Blood Platelets / cytology
  • Cell Line
  • Cell Proliferation
  • Disease Progression
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / metabolism
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Middle Aged
  • Philadelphia Chromosome
  • Piperazines / therapeutic use*
  • Pyrimidines / therapeutic use*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics*
  • Transcription, Genetic / genetics*
  • Transfection


  • Benzamides
  • Piperazines
  • Pyrimidines
  • RNA, Small Interfering
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl