The LNA EZN-3042 downregulatessurvivin expression and potentiates the chemotherapy killing curves in ALL cell lines. (a) Quantitative realtime PCR of total survivin mRNA expression in Molt4, Reh, MV4;11 and RS4;11 cells following transfection with antisurvivin (EZN-3042) LNA-ON or control (EZN-3046). Results are expressed as relative survivin mRNA expression compared with EZN-3046 treated (control) ±s.d. (n = 3). (b) Western blot analysis following transfection of Molt4 and Reh cells with EZN-3042 or EZN-3046. (c) Quantitative real-time PCR of survivin splice variants in Reh cells following transfection with antisurvivin (EZN-3042) LNA-ON or control (EZN-3046). Results are expressed as relative survivin mRNA expression compared with EZN-3046 treated (control) ±s.d. (n = 3). (d) Transfection of Molt4 cells with either the EZN-3042 or EZN-3046 alone or in combination with etoposide, doxorubicin or dexamethasone. Percentage of apoptosis is graphed relative to EZN-3046 in the absence of chemotherapeutic agent ±s.d. (*P<0.01, **P<0.0001). (e) Transfection of Reh, MV4;11 and RS4;11 cells with either EZN-3042 (filled shapes) or EZN-3046 (open shapes) in the presence of increasing doses of etoposide, doxorubicin and prednisolone. Percentage of survival is graphed relative to EZN-3046 in the absence of chemotherapeutic agent ±s.d. IC50 values for etopside (EZN3046, 3042 in µM: Reh 0.72, 9.3 × 10−4; MV4;11 0.6, 0.63 × 10−7; RS4;11 1.5, 0.28), doxorubicin (EZN-3046:3042 in nM: Reh 161, 85; MV4;11 253, 46; RS4;11 223, 145) and prednisolone (EZN-3046, 3042 in µg/ml: Reh 458, 248; MV4;11 922, 664; RS4;11 878, 483) in the presence and absence of survivin downregulation were determined by the Hill equation.