Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia
Menée à l'aide de xénogreffes, cette étude montre que l'inhibition de la survivine permet de surmonter l'apparition d'une résistance à la chimiothérapie dans la leucémie lymphoblastique aiguë
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. Here, 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, pharmacological knockdown 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 overcome drug resistance and prevent relapse in patients with ALL.