Figure 4. Effects of VLX1570 and L-asparaginase on protein synthesis.

[³H]-leucine incorporation into acid precipitable material was determined in cells exposed to drugs as indicated. (A) Time-dependent decrease in [³H]-leucine incorporation following exposure of SUP-B15 cells to VLX1570. (B) Dose-response of [³H]-leucine incorporation in ALL and non-ALL cell lines (6 hours drug exposure, [³H]-leucine added during the last hour). (C) [³H]-leucine incorporation in different ALL cell lines exposed to 0.16 μM VLX1570 and/or L-Asp for 6 hours ([³H]-leucine added after 5 h). Shown are average incorporation +/− S.E.M. from 5 samples. (D) Effect of Integrated Stress Response inhibitor (ISRIB; 0.2 μM) on [³H]-leucine incorporation in OPM-2 cells. (E, F) Effect of ISRIB on HSP70B’ expression in OPM-2 cells (E) and MOLT-4 cells (F). Cells were exposed to the indicated concentrations of VLX1570 in the presence or absence of 0.2 μM ISRIB. Proteins were extracted using RIPA buffer and processed for western blotting.