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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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
June 28, 2011
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| In: |
Blood
Year: 2011, Jahrgang: 118, Heft: 8, Pages: 2191-2199 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2011-04-351239 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2011-04-351239
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| Verfasserangaben: | 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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| 245 | 1 | 0 | |a Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia |c 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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| 520 | |a 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. | ||
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Combined Modality Therapy | |
| 650 | 4 | |a Drug Resistance, Neoplasm | |
| 650 | 4 | |a Gene Expression | |
| 650 | 4 | |a Gene Targeting | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Inhibitor of Apoptosis Proteins | |
| 650 | 4 | |a Mice | |
| 650 | 4 | |a Mice, Inbred NOD | |
| 650 | 4 | |a Mice, Knockout | |
| 650 | 4 | |a Neoplasm, Residual | |
| 650 | 4 | |a Oligonucleotides | |
| 650 | 4 | |a Precursor Cell Lymphoblastic Leukemia-Lymphoma | |
| 650 | 4 | |a Repressor Proteins | |
| 650 | 4 | |a RNA, Small Interfering | |
| 650 | 4 | |a Survivin | |
| 650 | 4 | |a Tumor Stem Cell Assay | |
| 650 | 4 | |a Xenograft Model Antitumor Assays | |
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| 700 | 1 | |a Kim, Yong-Mi |e VerfasserIn |4 aut | |
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