Abemaciclib exerts antiMCL efficacy by inhibiting cell cycle progression and inducing apoptosis, both in vitro and in vivo. (A-B) Expression of cell cycle regulators in primary patient samples with MCL (A) and MCL cell lines (B). (C) Abemaciclib inhibits cell viability after exposure to increasing concentrations of abemaciclib for 72 hours in MCL cell lines. The IC50 values are shown on the right. Data are presented as mean ± SD. The results are representative of 3 biological replicates. (D) Abemaciclib causes cell cycle arrest at G1 phase after exposure to abemaciclib for 24 hours. Data are indicated as mean ± SD. The results are representative of 3 biological replicates. (E) Representative immunoblot shows the downregulation of p-Rb after 12 hours of treatment with the same doses of abemaciclib shown in (D). (F) Abemaciclib induces dose-dependent apoptosis in MCL cell lines after 48 hours of treatment detected by annexin V/Propidium iodide-binding assay. Results are representative of 3 biological replicates. (G-H) Abemaciclib (10 mg/kg, 5 days per week) inhibits the tumor growth in patient-derived xenograft mouse models (derived from a patient resistant to CD19 CAR T-cell therapy). Tumor volume was monitored and plotted (G). Tumor weights and images at the end of the experiment are presented (H). SD, standard deviation.
