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Hedgehog signaling maintains chemoresistance in myeloid leukemic cells

Oncogene volume 29, pages 6314–6322 (2010)Cite this article

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Abstract

The development of resistance against chemotherapy remains one of the major challenges in the clinical management of leukemia. There is still limited insight into the molecular mechanisms that maintain the chemotherapy-resistant phenotype, despite the obvious clinical relevance that such knowledge would have. In this study, we show that the chemotherapy-resistant phenotype of myeloid leukemia cells correlates with activation of the Hedgehog (Hh) pathway, whereas in chemosensitive cells, such activation is less pronounced. Importantly, the overexpression of Hh pathway components induces chemoprotection and inhibition of the pathway reverts chemoresistance of Lucena-1 cells, apparently by interfering with P-glycoprotein-dependent drug resistance. Our data thus identify the Hh pathway as an essential component of multidrug resistance (MDR) myeloid leukemia and suggest that targeting the Hh pathway might be an interesting therapeutic avenue for overcoming MDR resistance in myeloid leukemia.

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Acknowledgements

KCS Queiroz is supported by the Maag-, Lever-, Darmstichting. CV Ferreira is supported by a research fellowship from CNPq. MP Peppelenbosch and CA Spek acknowledge the support of the Top-Institute pharma. We are grateful to Professor Vivian Rumjanek (Federal University of Rio de Janeiro) for donating Lucena-1 cells.

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Authors and Affiliations

  1. Department of Biochemistry, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil

    K C S Queiroz, R R Ruela-de-Sousa & C V Ferreira

  2. Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands

    K C S Queiroz, R R Ruela-de-Sousa, G M Fuhler & M P Peppelenbosch

  3. Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    K C S Queiroz, H L Aberson & C A Spek

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  1. K C S Queiroz
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  2. R R Ruela-de-Sousa
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  3. G M Fuhler
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  4. H L Aberson
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  5. C V Ferreira
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  6. M P Peppelenbosch
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Correspondence to K C S Queiroz.

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Queiroz, K., Ruela-de-Sousa, R., Fuhler, G. et al. Hedgehog signaling maintains chemoresistance in myeloid leukemic cells. Oncogene 29, 6314–6322 (2010). https://doi.org/10.1038/onc.2010.375

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