4.6 Article

Additive antileukemia effects by GFI1B- and BCR-ABL-specific siRNA in advanced phase chronic myeloid leukemic cells

Journal

CANCER GENE THERAPY
Volume 20, Issue 7, Pages 421-427

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2013.31

Keywords

advanced leukemia; BCR-ABL; GFI1B; K562; small interfering RNA

Funding

  1. Forderverein Essener Tumorklinik e.V.
  2. Kulturstiftung Essen e.V.

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available