Figure 6.
Role of RARγ in MM cell sensitivity to Cfz treatment. Gene-profiling data from Mulligan et al study was analyzed. (A) PFS and (B) OS curves were evaluated in Btz-treated patients with MM based on high-RARγ (red, RARγhigh) or low-RARγ (black, RARγlow) expression in MM cells. The cutoff threshold was defined by the MaxStat package. (C-D) Gene-profiling data from MMRF coMMpass study were analyzed. PFS (C) and OS curves (D) were evaluated in newly diagnosed patients with MM treated with PI-based regimens as first-line treatment based on high-RARγ (blue, RARγhigh) or low-RARγ (red, RARγlow) expression in MM cells. (E) Summary results of apoptosis of WT KMS-11 and KMS-11/Cfz MM cells with indicated treatment for 24 hours. (F) Summary results of apoptosis of primary MM cells treated with DMSO, BMS961, Cfz, or their combinations (BMS+Cfz). (G) Histogram showing mRNA expression of IRF1 (left panel) and OAS1 (right panel) in ARP-1 or MM.1S cells treated with DMSO, BMS961, Cfz, or their combinations for 12 hours. (H) Western blot of IRF1 and OAS1 expression in ARP-1 or MM.1S cells treated with DMSO, BMS961, Cfz, or their combinations for 16 hours. (I) RNA integrity of ARP-1 (left panel) or MM.1S (right panel) cells treated with DMSO, BMS961, Cfz, or their combinations (BMS+Cfz) for 16 hours. The survival plots in panels A to D show Kaplan-Meier estimates of survival and comparisons using the log-rank test. Student t test was used to compare 2 samples. *P < .05; **P < .01; ***P < .001; ***P < .0001.