Additive antileukemia effects by GFI1B- and BCR-ABL-specific siRNA in advanced phase chronic myeloid leukemic cells Journal Article
| Authors: | Koldehoff, M.; Zakrzewski, J. L.; Beelen, D. W.; Elmaagacli, A. H. |
| Article Title: | Additive antileukemia effects by GFI1B- and BCR-ABL-specific siRNA in advanced phase chronic myeloid leukemic cells |
| Abstract: | Previous studies demonstrated selective inhibition of the BCR-ABL (breakpoint cluster region-Abelson murine leukemia oncogene) tyrosine kinase by RNA interference in leukemic cells. In this study, we evaluated the effect of BCR-ABL small interfering RNA (siRNA) and GFI1B siRNA silencing on chronic myeloid leukemia (CML) cells in myeloid blast crises. The GFI1B gene was mapped to chromosome 9 and is, therefore, located downstream of the BCR-ABL translocation in CML cells. Co-transfection of BCR-ABL siRNA and GFI1B siRNA dramatically decreased cell viability and significantly induced apoptosis and inhibited proliferation in K562 cells (P<0.0001) and primary advanced phase CML cells (P<0.0001) versus controls. Furthermore, combining of BCR-ABL siRNA and GFI1B siRNA significantly modified the expression of several relevant genes including Myc, MDR1, MRP1 and tyrosyl-phosphoproteins in primary CML cells. Our data suggest that silencing of both BCR-ABL siRNA and GFI1B siRNA is associated with an additive antileukemic effect against K562 cells and primary advanced CML cells, further validating these genes as attractive therapeutic targets. © 2013 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; gene translocation; human cell; advanced cancer; cell proliferation; cell viability; apoptosis; gene expression; small interfering rna; transcription factor; antineoplastic activity; in vitro study; chronic myeloid leukemia; cancer inhibition; gene mapping; genetic transfection; leukemia cell; murinae; bcr abl protein; gene silencing; phosphoprotein; oncogene myc; bcr-abl; chromosome 9; multidrug resistance protein 1; k562; growth factor independent 1b protein; gfi1b; advanced leukemia |
| Journal Title: | Cancer Gene Therapy |
| Volume: | 20 |
| Issue: | 7 |
| ISSN: | 0929-1903 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-07-01 |
| Start Page: | 421 |
| End Page: | 427 |
| Language: | English |
| DOI: | 10.1038/cgt.2013.31 |
| PROVIDER: | scopus |
| PUBMED: | 23788109 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2013" - "CODEN: CGTHE" - "Source: Scopus" |
