Page 164 - Haematologica Vol. 110 - January 2025

ARTICLE - Targeted CDK7 and BRD4 inhibition in myeloma AB
Y. Yao et al.
CD
E
Figure 1. Enhanced suppression of multiple myeloma cell proliferation through dual in- hibition strategy. (A, B) A panel of 11 multiple myeloma cell lines was treated with YKL-5- 124 or JQ1 alone or in combination, and cell survival was assessed by a CellTiter-Glo up- take assay. For a representative cell line (MM1S), the percentage of cell viability com- pared to untreated cells is shown (mean ± standard deviation [SD]; N=3) (A). Synergism analysis was performed with Calcusyn soft- ware. A Combination Index (CI)=1 means an additive effect, a CI <1 means a synergistic effect, and a CI >1 means an antagonistic effect (B). ***P<0.001, ****P<0.0001. (C, D) XG1 cells were cultured in the presence of different concentrations of YKL-5-124 with or without JQ1 for 72 hours, and cell surviv- al was assessed by a CellTiter-Glo uptake assay. Data are presented as the percentage of cell viability compared to untreated cells (mean ± SD; N=3) (C). Synergism analysis was performed with Calcusyn software (D). *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. (E, F) IM9, RPMI8226 and H929 cells were cultured in the presence of the BRD4 inhib- itor ARV-825 (E) or the BRD4 degrader I-BET151 (F) with or without YKL-5-124. Cell viability was assessed by a CCK8 assay (mean ± SD; N=3). *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.
F
Haematologica | 110 January 2025
156