Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia

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, Yong Mi Kim

Research output: Contribution to journalArticle

72 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2191-2199
Number of pages9
JournalBlood
Volume118
Issue number8
DOIs
StatePublished - Aug 25 2011

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug Resistance
Chemotherapy
Pharmaceutical Preparations
Inhibitor of Apoptosis Proteins
Combination Drug Therapy
Antisense Oligonucleotides
Heterografts
Small Interfering RNA
Recurrence
Residual Neoplasm
Leukemia
Survival

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Park, E., Gang, E. J., Hsieh, Y. T., Schaefer, P., Chae, S., Klemm, L., ... Kim, Y. M. (2011). Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia. Blood, 118(8), 2191-2199. https://doi.org/10.1182/blood-2011-04-351239

Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia. / Park, Eugene; Gang, Eun Ji; Hsieh, Yao Te; Schaefer, Paul; Chae, Sanna; Klemm, Lars; Huantes, Sandra; Loh, Mignon; Conway, Edward M.; Kang, Eun Suk; Koo, Hong Hoe; Hofmann, Wolf Karsten; Heisterkamp, Nora; Pelus, Louis; Keerthivasan, Ganesan; Crispino, John; Kahn, Michael; Müschen, Markus; Kim, Yong Mi.

In: Blood, Vol. 118, No. 8, 25.08.2011, p. 2191-2199.

Research output: Contribution to journalArticle

Park, E, Gang, EJ, Hsieh, YT, Schaefer, P, Chae, S, Klemm, L, Huantes, S, Loh, M, Conway, EM, Kang, ES, Koo, HH, Hofmann, WK, Heisterkamp, N, Pelus, L, Keerthivasan, G, Crispino, J, Kahn, M, Müschen, M & Kim, YM 2011, 'Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia', Blood, vol. 118, no. 8, pp. 2191-2199. https://doi.org/10.1182/blood-2011-04-351239
Park E, Gang EJ, Hsieh YT, Schaefer P, Chae S, Klemm L et al. Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia. Blood. 2011 Aug 25;118(8):2191-2199. https://doi.org/10.1182/blood-2011-04-351239
Park, Eugene ; Gang, Eun Ji ; Hsieh, Yao Te ; Schaefer, Paul ; Chae, Sanna ; Klemm, Lars ; Huantes, Sandra ; Loh, Mignon ; Conway, Edward M. ; Kang, Eun Suk ; Koo, Hong Hoe ; Hofmann, Wolf Karsten ; Heisterkamp, Nora ; Pelus, Louis ; Keerthivasan, Ganesan ; Crispino, John ; Kahn, Michael ; Müschen, Markus ; Kim, Yong Mi. / Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia. In: Blood. 2011 ; Vol. 118, No. 8. pp. 2191-2199.
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