Back to Search
Start Over
Silencing of miR-21 sensitizes CML CD34+ stem/progenitor cells to imatinib-induced apoptosis by blocking PI3K/AKT pathway.
- Source :
-
Leukemia Research . Oct2015, Vol. 39 Issue 10, p1117-1124. 8p. - Publication Year :
- 2015
-
Abstract
- BCR-ABL tyrosine kinase inhibitor imatinib fails to eradicate leukemia stem cells (LSCs), the underlying mechanisms maintaining CML LSCs remain poorly understood. Here, we showed that transient inhibition of miR-21 by antagomiR-21 markedly increased imatinib-induced apoptosis in CML, but not normal CD34 + stem/progenitor cells. Furthermore, PI3K inhibitors also significantly sensitized CML CD34 + cells to imatinib-induced apoptosis. MiR-21 or PI3K inhibitor in combination with imatinib treatment significantly decreased AKT phosphorylation and c-Myc expression than either agent did alone, but did not affect Bim and Bcl-6 expresssion. These findings indicate that miR-21 is required for maintaining the imatinib-resistant phenotype of CML CD34 + cells through PI3K/AKT signaling pathway, thus providing the basis for a promising therapeutic approach to eliminate CML LSCs. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01452126
- Volume :
- 39
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Leukemia Research
- Publication Type :
- Academic Journal
- Accession number :
- 109446162
- Full Text :
- https://doi.org/10.1016/j.leukres.2015.07.008