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Chronic Lymphocytic Leukemia

Gene knockdown studies revealed CCDC50 as a candidate gene in mantle cell lymphoma and chronic lymphocytic leukemia

Leukemia volume 23, pages 2018–2026 (2009)Cite this article

Abstract

The two B-cell non-Hodgkin's lymphoma entities, chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), show recurrent chromosomal gains of 3q25–q29, 12q13–q14 and 18q21–q22. The pathomechanisms affected by these aberrations are not understood. The aim of this study was to identify genes, located within these gained regions, which control cell death and cell survival of MCL and CLL cancer cells. Blood samples collected from 18 patients with CLL and 6 patients with MCL, as well as 6 cell lines representing both malignancies were analyzed by gene expression profiling. By a comparison of genomic DNA and gene expression, 72 candidate genes were identified. We performed a limited RNA interference screening with these candidates to identify genes affecting cell survival. CCDC50 (coiled coil domain containing protein 50), SERPINI2 and SMARCC2 mediated a reduction of cell viability in primary CLL cells as well as in cell lines. Gene knockdown and a nuclear factor kappa B (NFκB) reporter gene assay revealed that CCDC50 is required for survival in MCL and CLL cells and controls NFκB signaling.

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Acknowledgements

We thank Dr Michael Rogers for helpful discussions and a critical review of this paper, Professor Reiner Siebert and Dr Inga Vater from the University of Kiel for kindly providing additional MCL patient material, Verena Gschwend and Angela Schulz for brilliant laboratory support and Dr Ludger Altrogge (Lonza, Cologne, Germany) for the excellent collaboration and technical support. This study is supported by the German José-Carreras leukemia foundation (DJCLS R 06/13v) (DJCLS R 08/22v) and the Fritz Thyssen foundation (10.04.1.169). MB is funded by the Helmholtz Alliance for Systems Biology. AR and EH are supported by the Interdisciplinary Center for Clinical Research (IZKF), University of Würzburg, Germany. GO is supported by the Robert-Bosch-Foundation.

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Authors and Affiliations

  1. Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany

    A Farfsing, F Engel, M Seiffert, P Lichter & A Pscherer

  2. Institute of Pathology, Junior Research Group ‘Functional Genomics‘, University of Wurzburg, Wurzburg, Germany

    E Hartmann, G Ott & A Rosenwald

  3. Department of Internal Medicine III, University hospital Ulm, Ulm, Germany

    S Stilgenbauer & H Döhner

  4. Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and University of Heidelberg, Heidelberg, Germany

    M Boutros

  5. Institute of Clinical Pathology, Robert-Bosch-Hospital, Stuttgart, Germany

    G Ott

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  1. A Farfsing
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  2. F Engel
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  3. M Seiffert
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Correspondence to P Lichter.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Farfsing, A., Engel, F., Seiffert, M. et al. Gene knockdown studies revealed CCDC50 as a candidate gene in mantle cell lymphoma and chronic lymphocytic leukemia. Leukemia 23, 2018–2026 (2009). https://doi.org/10.1038/leu.2009.144

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