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 [Leuk Res] 2015 Oct; Vol. 39 (10), pp. 1117-24. Date of Electronic Publication: 2015 Jul 21. - 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.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adult
Antigens, CD34 immunology
Child
Female
Gene Silencing
Humans
Imatinib Mesylate pharmacology
Infant
Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism
Male
Middle Aged
Neoplastic Stem Cells metabolism
Neoplastic Stem Cells pathology
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors pharmacology
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Real-Time Polymerase Chain Reaction
Transfection
Young Adult
Antineoplastic Agents pharmacology
Apoptosis drug effects
Apoptosis physiology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
MicroRNAs antagonists & inhibitors
Neoplastic Stem Cells drug effects
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5835
- Volume :
- 39
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Leukemia research
- Publication Type :
- Academic Journal
- Accession number :
- 26248946
- Full Text :
- https://doi.org/10.1016/j.leukres.2015.07.008