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All common p210 and p190 Bcr-abl variants can be targeted by RNA interference

Leukemia volume 19, pages 290–292 (2005)Cite this article

TO THE EDITOR

RNA interference (RNAi) is a cellular mechanism that utilizes the ability of double-stranded RNA (dsRNA) to interfere with homologous gene expression at the RNA or DNA level. Recent developments in the use of small interfering RNA (siRNA) to inhibit specific gene expression in mammalian cells have highlighted the potential of these molecules as a therapeutic agent (reviewed in Novina and Sharp1). Fusion transcripts encoding oncogenic proteins such as Bcr-abl represent ideal targets for a disease-specific RNAi approach. There are different clinically relevant bcr-abl transcript variants: in about 95% of the CML patients, the bcr-abl fusion transcripts e14a2 (former b3a2) and e13a2 (former b2a2) can be detected. The translated product is in each case a p210 kDa Bcr-abl protein. In patients with Ph+ ALL, a shorter transcript version called bcr-abl-e1a2 predominates (reviewed in Kurzrock et al2). Translation of this variant results in the somewhat smaller p190 kDa Bcr-abl protein. The possibility to use RNAi for the selective degradation of the bcr-abl-e14a2 transcript variant has been demonstrated recently.3, 4, 5, 6 Nevertheless, it is unclear so far whether the expression of the other two relevant bcr-abl transcripts (e13a2 and e1a2) can also be similarly downregulated. We therefore investigated the activity of a panel of siRNAs directed to the bcr-abl transcript variants e13a2 and e1a2.

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Acknowledgements

This work was financially supported by the Robert Bosch foundation Project No. 11.5.8002.0006.1.

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Authors and Affiliations

  1. Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    L Wohlbold, H van der Kuip & A Moehring

  2. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

    G Granot & M Oren

  3. Alnylam Europe AG, Kulmbach, Germany

    H-P Vornlocher

  4. 2nd Department of Internal Medicine, Oncology and Hematology, Robert Bosch Hospital, Stuttgart, Germany

    W E Aulitzky

Authors
  1. L Wohlbold
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  2. H van der Kuip
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  4. G Granot
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  5. M Oren
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  6. H-P Vornlocher
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  7. W E Aulitzky
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Correspondence to W E Aulitzky.

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Wohlbold, L., van der Kuip, H., Moehring, A. et al. All common p210 and p190 Bcr-abl variants can be targeted by RNA interference. Leukemia 19, 290–292 (2005). https://doi.org/10.1038/sj.leu.2403603

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