Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia.
Blood
; 118(8): 2191-9, 2011 Aug 25.
Article
in En
| MEDLINE
| ID: mdl-21715311
ABSTRACT
Relapse of drug-resistant acute lymphoblastic leukemia (ALL) has been associated with increased expression of survivin/BIRC5, an inhibitor of apoptosis protein, suggesting a survival advantage for ALL cells. In the present study, we report that inhibition of survivin in patient-derived ALL can eradicate leukemia. Targeting survivin with shRNA in combination with chemotherapy resulted in no detectable minimal residual disease in a xenograft model of primary ALL. Similarly, pharmacologic knock-down of survivin using EZN-3042, a novel locked nucleic acid antisense oligonucleotide, in combination with chemotherapy eliminated drug-resistant ALL cells. These findings show the importance of survivin expression in drug resistance and demonstrate that survivin inhibition may represent a powerful approach to overcoming drug resistance and preventing relapse in patients with ALL.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Inhibitor of Apoptosis Proteins
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Blood
Year:
2011
Document type:
Article
Affiliation country:
United States