期刊
LEUKEMIA
卷 23, 期 11, 页码 2018-2026出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2009.144
关键词
B-cell chronic lymphocytic leukemia; mantle cell lymphoma; siRNA screen; functional assays in primary CLL cells; CCDC50
资金
- German Jose-Carreras leukemia foundation [DJCLS R 06/13v, DJCLS R 08/22v]
- Fritz Thyssen foundation [10.04.1.169]
- Helmholtz Alliance for Systems Biology
- Interdisciplinary Center for Clinical Research (IZKF)
- University of Wurzburg, Germany
- Robert-Bosch-Foundation
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 (NF kappa B) reporter gene assay revealed that CCDC50 is required for survival in MCL and CLL cells and controls NF kappa B signaling. Leukemia (2009) 23, 2018-2026; doi:10.1038/leu.2009.144; published online 30 July 2009
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