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Oncogenes, Fusion Genes and Tumor Suppressor Genes

Revealing the role of TEL/AML1 for leukemic cell survival by RNAi-mediated silencing

Leukemia volume 25, pages 313–320 (2011)Cite this article

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Abstract

Translocation (12;21), the most frequent chromosomal aberration in childhood acute lymphoblastic leukemia, creates TEL/AML1 fusion gene. Resulting hybrid protein was shown to have a role in pre-leukemia establishment. To address its role for leukemic cell survival, we applied RNA interference to silence TEL/AML1 in leukemic cells. We designed and tested 11 different oligonucleotides targeting the TEL/AML1 fusion site. Using most efficient siRNAs, we achieved an average of 74–86% TEL/AML1 protein knockdown in REH and UOC-B6 leukemic cells, respectively. TEL/AML1 silencing neither decreased cell viability, nor induced apoptosis. On the contrary, it resulted in the modest but significant increase in the S phase fraction and in higher proliferation rate. Opposite effects on cell cycle distribution and proliferation were induced by AML1 silencing, thus, supporting our hypothesis that TEL/AML1 may block AML1-mediated promotion of G1/S progression through the cell cycle. In line with the lack of major effect on phenotype, we found no significant changes in clonogenic potential and global gene expression pattern upon TEL/AML1 depletion. Our data suggest that though TEL/AML1 is important for the (pre)leukemic clone development, it may be dispensable for leukemic cell survival and would not be a suitable target for gene-specific therapy.

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Acknowledgements

This work was supported by grants MSM0021620813 and MZ0FNM2005.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, CLIP, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic

    M Zaliova, J Madzo & J Trka

  2. Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany

    G Cario

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  1. M Zaliova
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  2. J Madzo
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  3. G Cario
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  4. J Trka
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Correspondence to M Zaliova.

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Zaliova, M., Madzo, J., Cario, G. et al. Revealing the role of TEL/AML1 for leukemic cell survival by RNAi-mediated silencing. Leukemia 25, 313–320 (2011). https://doi.org/10.1038/leu.2010.277

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