Aurora kinases in childhood acute leukemia: The promise of aurora B as therapeutic target
- Hartsink-Segers, S.
- Zwaan, Michel
- Exalto, Carla
- Luijendijk, Mirjam
- Calvert, V.
- Petricoin, Emanuel F.
- Evans, William
- Reinhardt, Dirk
- Haas, Valerie
- Hedtjärn, M.
- Hansen, B.
- Koch, T.
- Caron, Huib
- Pieters, Rob
- Boer, Monique
DOIAbstract
textabstractWe investigated the effects of targeting the mitotic regulators aurora kinase A and B in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Aurora protein expression levels in pediatric ALL and AML patient samples were determined by western blot and reverse phase protein array. Both kinases were overexpressed in ALL and AML patients (P<0.0002), especially in E2A-PBX1-translocated ALL cases (P<0.002), compared with normal bone-marrow mononuclear cells. Aurora kinase expression was silenced in leukemic cell lines using short hairpin RNAs and locked nucleic acid-based mRNA antagonists. Aurora B knockdown resulted in proliferation arrest and apoptosis, whereas aurora A knockdown caused no or only minor gr...
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