Gene-expression changes in MM cells treated with FGFR3 inhibitors. (A) Venn diagram details genes differentially altered in KMS11 myeloma cells at least 2-fold following treatment with an FGFR3-selective kinase inhibitor compared with vehicle control. Eight hundred and forty five genes were commonly dysregulated (Tables S1-S3). (B) Venn diagram maps the 2-fold differentially altered genes using FGFR3 knockdown by siRNA in KMS11 cells or chemical modulation and the 121 genes altered at least 1.5-fold following FGF ligand stimulation in UTMC2 myeloma cells (containing wild-type FGFR3 and no RAS mutations). Ten genes were found to be differentially altered under this model under all 5 experimental conditions. (C) The apoptotic effect of PD173074 and CHIR258 on KMS11 cells is not marked at 48 hours. As shown here, no increase in annexin V-positive cells is seen with PD173074 even at 72 hours compared with controls, while only early evidence of apoptosis is seen with CHIR258. Error bars show standard deviation in replicate of 3 experiments.