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Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia

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 eradi...

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Main Authors: Park, Eugene (Author) , Gang, Eun Ji (Author) , Hsieh, Yao-Te (Author) , Schaefer, Paul (Author) , Chae, Sanna (Author) , Klemm, Lars (Author) , Huantes, Sandra (Author) , Loh, Mignon (Author) , Conway, Edward M. (Author) , Kang, Eun-Suk (Author) , Hoe Koo, Hong (Author) , Hofmann, Wolf-Karsten (Author) , Heisterkamp, Nora (Author) , Pelus, Louis (Author) , Keerthivasan, Ganesan (Author) , Crispino, John (Author) , Kahn, Michael (Author) , Müschen, Markus (Author) , Kim, Yong-Mi (Author)
Format: Article (Journal)
Language:English
Published: June 28, 2011
In: Blood
Year: 2011, Volume: 118, Issue: 8, Pages: 2191-2199
ISSN:1528-0020
DOI:10.1182/blood-2011-04-351239
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2011-04-351239
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Author Notes:Eugene Park, Eun Ji Gang, Yao-Te Hsieh, Paul Schaefer, Sanna Chae, Lars Klemm, Sandra Huantes, Mignon Loh, Edward M. Conway, Eun-Suk Kang, Hong Hoe Koo, Wolf-Karsten Hofmann, Nora Heisterkamp, Louis Pelus, Ganesan Keerthivasan, John Crispino, Michael Kahn, Markus Müschen, and Yong-Mi Kim
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Summary: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.
Item Description:Gesehen am 09.09.2022
Physical Description:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2011-04-351239

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