BMS961 enhances Cfz-killing effect of human MM cells in vivo. (A-F) NSG mice were injected IV with 2 × 10⁶ MM.1S-luc MM cells. At day 16 after tumor establishment, DMSO, ATRA, or BMS961 (15 mg/kg for every 3 days), Cfz (3 mg/kg for 2 consecutive days weekly), ATRA+Cfz, or BMS961+Cfz were injected into MM-bearing mice (n ≥ 4 for each group). Blood samples were collected weekly starting at day 16. In vivo bioluminescent imaging (A) and quantification of bioluminescence intensity (B) showing tumor burden in MM-bearing mice treated with DMSO, ATRA, BMS961, Cfz, ATRA+Cfz, or BMS961+Cfz. Tumor burden (C), analyzed by enzyme-linked immunosorbent assay measuring human immunoglobulin light chain in mouse plasma which was normalized to control, and survival (D) in MM-bearing mice were calculated. (E-F) RNA gel electrophoresis showing ex vivo RNA integrity of CD138⁺ MM cells sorted out from MM.1S-bearing NSG mice received the indicated treatments (A+C: ATRA+Cfz, and B+C: BMS961+Cfz; n = 3 for each group) for 1 day. The positions of 18S and 28S ribosomal RNA are indicated. (G) Tumor burden and (H) survival of NSG mice bearing CTR-KD (dashed line) or RARγ-KD (solid line) ARP-1 cells receiving the indicated treatments (n = 5 for each group). Tumor bioluminescence intensity and burden were analyzed by 2-way analysis of variance. The survival plot showing Kaplan-Meier estimates of survival and comparisons using the log-rank test. For panel E, representative results of 3 are shown. Student t test was used to compare 2 samples. Veh., vehicle. *P < .05; **P < .01; ***P < .001; ****P < .0001.