Fig. 5.
NRAS-G12D mutation confers resistance to VEN and sensitivity to MCL-1 inhibition. a, b The BaF3 cells expressing NRAS-WT (dotted lines) or NRAS-G12D (solid lines) were treated with VEN (a) or indicated MCL-1 inhibitors S63845 or AZD5991 (b) for 24 h, after which cell viability was determined by CellTiter-Glo assay. Luminescence reads were normalized to those of DMSO-treated control cells. Data represent mean ± SD from triplicate independent experiments. c MOLM-13 cells expressing NRAS-G12D were treated with indicated inhibitor for 24 h, then cell viability was determined by CellTiter-Glo assay. Luminescence reads were normalized to those of DMSO-treated control cells. Data are mean ± SD. d Spleen harvested from mice received vehicle, AZD5991, VEN, or the combination of AZD5991 and VEN. One spleen from a healthy mouse is shown for comparison. e Weight of spleens collected from each group. Data are mean ± SD. f Tumor burden shown by %hCD45 from spleens (SP), bone marrows (BM) and livers from each mouse in specified cohort. Data are mean ± SD. g H&E staining of SP, BM, and liver from one representative mouse from each group