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

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...

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Bibliographic Details
Published in:Clinical and experimental medicine 2007-06, Vol.7 (2), p.47-55
Main Authors: Koldehoff, M, Steckel, N K, Beelen, D W, Elmaagacli, A H
Format: Article
Language:English
Subjects:
Benzamides
Blood Cell Count
Blood Platelets - cytology
Cell Line
Cell Proliferation
Chemotherapy
Disease Progression
Drug resistance
Drug Resistance, Neoplasm - drug effects
Feasibility studies
Female
Fusion Proteins, bcr-abl - genetics
Fusion Proteins, bcr-abl - metabolism
Gene expression
Gene Expression Regulation, Neoplastic
Gene therapy
Genetic Therapy
Humans
Imatinib Mesylate
Leukemia
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
Oncology
Philadelphia Chromosome
Piperazines - therapeutic use
Pyrimidines - therapeutic use
Ribonucleic acid
RNA
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
Transcription, Genetic - genetics
Transfection
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Summary: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.
ISSN:1591-8890
1591-9528
DOI:10.1007/s10238-007-0125-z