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Blood. 2011 Aug 25;118(8):2191-9. doi: 10.1182/blood-2011-04-351239. Epub 2011 Jun 28.

Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia.

Author information

  • 1Department of Pediatrics, Division of Hematology and Oncology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.

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.

PMID:
21715311
[PubMed - indexed for MEDLINE]
PMCID:
PMC3162353
Free PMC Article

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