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Silencing of miR-21 sensitizes CML CD34+ stem/progenitor cells to imatinib-induced apoptosis by blocking PI3K/AKT pathway
- Source :
- Leukemia Research. 39:1117-1124
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 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.
- Subjects :
- Adult
Male
Cancer Research
medicine.drug_class
Antigens, CD34
Antineoplastic Agents
Apoptosis
Biology
Real-Time Polymerase Chain Reaction
Transfection
Tyrosine-kinase inhibitor
Young Adult
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
hemic and lymphatic diseases
medicine
Humans
Gene Silencing
Progenitor cell
Child
Protein Kinase Inhibitors
neoplasms
PI3K/AKT/mTOR pathway
Phosphoinositide-3 Kinase Inhibitors
Akt/PKB signaling pathway
Infant
Imatinib
Hematology
Middle Aged
MicroRNAs
Imatinib mesylate
Oncology
Imatinib Mesylate
Neoplastic Stem Cells
Cancer research
Female
Signal transduction
Stem cell
Proto-Oncogene Proteins c-akt
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 01452126
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Leukemia Research
- Accession number :
- edsair.doi.dedup.....1128e448a291532a1adbdf48b2a21e81