1. Silencing of ROR1 and FMOD with siRNA results in apoptosis of CLL cells.
- Author
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Choudhury A, Derkow K, Daneshmanesh AH, Mikaelsson E, Kiaii S, Kokhaei P, Osterborg A, and Mellstedt H
- Subjects
- Extracellular Matrix Proteins biosynthesis, Fibromodulin, Genes, Neoplasm, Humans, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, Proteoglycans biosynthesis, RNA, Neoplasm genetics, RNA, Small Interfering genetics, Receptor Tyrosine Kinase-like Orphan Receptors biosynthesis, Reverse Transcriptase Polymerase Chain Reaction methods, Transfection, Tumor Cells, Cultured, Apoptosis genetics, Extracellular Matrix Proteins genetics, Gene Silencing, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Proteoglycans genetics, Receptor Tyrosine Kinase-like Orphan Receptors genetics
- Abstract
We have previously demonstrated that ROR1 and FMOD (fibromodulin) are two genes upregulated in chronic lymphocytic leukaemia (CLL) cells compared to normal blood B cells. In this study, siRNAs were used to specifically silence ROR1 and FMOD expression in CLL cells, healthy B cells and human fibroblast cell lines. siRNA treatment induced a specific reduction (75-95%) in FMOD and ROR1 mRNA. Western blot analysis with specific antibodies for FMOD and ROR1 demonstrated that the proteins were significantly downregulated 48 h after siRNA treatment. Silencing of FMOD and ROR1 resulted in statistically significant (P ≤ 0·05-0·001) apoptosis of CLL cells but not of B cells from normal donors. Human fibroblast cell lines treated with FMOD and ROR1 siRNA did not undergo apoptosis. This is the first report demonstrating that ROR1 and FMOD may be involved in the survival of CLL cells. ROR1 in particular is further explored as potential target for therapy in CLL., (© 2010 Blackwell Publishing Ltd.)
- Published
- 2010
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