BCMA and its ligands APRIL and BAFF are upregulated in MM and support the growth and survival of MM in vivo. (A) BCMA mRNA transcript validated in patient myeloma cells (n = 11) and plasma cells harvested from healthy donors (n = 6); P = 0.0001. (B) Serum APRIL level detected in MM patients (n = 11) compared with healthy donors (n = 8) through ELISA; P = 0.001. (C) Serum BAFF level detected in MM patients (n = 11) compared with healthy donors (n = 8) through ELISA; P = 0.0028. (D) Subcutaneous tumor growth of INA-6 MM cells with stably transfected dox-inducible BCMA KO shRNA (n = 8) or scramble shRNA (n = 7) in 6-wk-old female NSG mice; P = 0.0005. (E) Comparing tumor weights of terminally harvested mice inoculated with dox-inducible shSCRM (n = 7) and shBCMA (n = 8) in INA-6 MM tumor cells; P = 0.0005. (F) Representative images of Ki67-positive cells in the harvested tumors of dox-inducible shSCRM and shBCMA, analyzed by immunohistochemical (IHC) staining. Scale bar, 50 μm. (G) Quantitative analysis of Ki67-positive cells in the harvested tumors of dox-inducible shSCRM and shBCMA, represented as the average number of positive nuclei per image field; P = 0.0008. (H) Representative images of TUNEL-positive cells in the harvested tumors of dox-inducible shSCRM and shBCMA, analyzed by IHC staining. Scale bar, 50 μm. (I) Quantitative analysis of TUNEL-positive cells in the harvested tumors of dox-inducible shSCRM and shBCMA, represented as the average number of positive nuclei per image field; P = 0.0002. (J) Total human M protein (paraprotein) detected in the serum of NSG mice inoculated with dox-inducible shSCRM and shBCMA human INA-6 MM tumor cells harvested terminally (n = 3); P = 0.0268. Statistical analysis was conducted using one-way ANOVA for comparing between treatment groups and repeated ANOVA for changes occurring over time. *, P < 0.05; **, P < 0.01; ***, P < 0.001.