Page 229 - 2021_09-Haematologica-web

Letters to the Editor
Figure 1. Concurrent MCL-1 and HDAC inhibition synergistically kills multiple myeloma cells in vitro via apoptosis induction. Cell viability of MM1.S cells 96 hours (h) after treatment with S63845 (A and D), venetoclax (B and E), A-1331952 (C and F) alone or in combination with either panobinostat (A to C) or ricol- inostat (D to F). Results are presented relative to 0.1% dimethyl sulfoxide (DMSO) control. The combination index was calculated and stated as a range. Combination index values of <0.8, 0.8–1.2, and >1.2 were interpreted as synergistic, additive, and antagonistic drug activity, respectively. Apoptosis induction in MM.1S, U266 and KMS-12-BM cells was assessed by 7AAD/Annexin V staining 72 h after treatment in the absence (G to I) or presence of MSCT+ stromal cells (J to L). (M) Cytochrome c release assay was performed 24 h after treatment initiation at the indicated concentrations. One representative experiment of two is shown. (N) Assessment of cleaved caspase 3 and cleaved PARP via flow cytometry was performed 48 h or 72 h post treatment induction, respectively. Error bars indicate standard deviation of the mean (SDM) of triplicate experiments. Differences between groups were calculated with one-way ANOVA, corrected for multiple comparison with Bonferroni-Holm correction with ****P<0.0001, **P<0.001 and *P<0.05.
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Figure 2. Legend on following page.
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