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. 2013 Dec;98(12):1905–1911. doi: 10.3324/haematol.2013.093823

Figure 3.

Figure 3.

MCL1 silencing together with glycolysis inhibition synergistically inhibits leukemic cell survival and concomitantly sensitizes to prednisolone. (A) Leukemic cell survival of a MLL-AF4+ BCP-ALL, ETV6-RUNX1+ BCP-ALL, E2A-PBX1+ BCP-ALL, ETP-ALL and tetraploid T-ALL cell line after treatment with MCL1 LNA-b and/or 0.5mM 2-DG for 168 h, compared to non-silencing control LNA (NSC, set at 100%). Data are presented as means plus SEM of 3 (ETV6-RUNX1+ BCP-ALL and Tetraploid T-ALL) or 2 independent experiments (*P<0.05, **P<0.01, ***P<0.001). Fsyn represents the synergy factor, where <1 indicates synergy. (B) Leukemic cell survival after prednisolone exposure for three days, i.e. 96 till 168 h after start of MCL1 LNA-b and/or 0.5mM 2-DG in equivalent cell lines as in panel (A). Data were compared to a non-silencing control LNA (NSC) without prednisolone (see also panel (A), set to 100%), to visualize the total effect on cell survival after prednisolone. Data are presented as means plus SEM of 3 (ETV6-RUNX1+ BCP-ALL and Tetraploid T-ALL) or 2 independent experiments (*P<0.05, **P<0.01, ***P<0.001). (C) Sensitivity of leukemic cells to prednisolone was measured in a 3-day MTT assay from t96 to t168 after treatment with MCL1 LNA-b and/or a non-silencing control LNA (NSC) with or without 0.5mM 2-DG. Cell survival depicted on the y-axis was corrected for cell death induced by MCL1 knockdown and 0.5mM 2-DG itself in the absence of prednisolone, to visualize the absolute prednisolone effects. Data are presented as means plus SEM of 3 (ETV6-RUNX1+ BCP-ALL and Tetraploid T-ALL) or 2 independent experiments (*P<0.05, **P<0.01, ***P<0.001).