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. Author manuscript; available in PMC: 2023 Jul 25.
Published in final edited form as: Oncogene. 2023 Apr 8;42(21):1751–1762. doi: 10.1038/s41388-023-02684-9

Figure 7. Group B and Group A VQ cells display distinct responses to bortezomib in vivo.

Figure 7.

(A) Gene set enrichment analysis (GSEA) of KEGG_ NF-kappa B signaling pathway and Hallmark_TNFA signaling via NFKB between Group A (VQ-D1/D4) and Group B (VQ-D2/D5) myeloma cells. (B) Transcript levels of NF-ĸB related genes Tnfaip3, CD74, and Il2rg in CD138+ B220− cells from Group A and B VQ myeloma mice. VQ donor of origin is color-coded as indicated. Results are presented as mean + SD. Two-sided t-Test was performed. FPKM, Fragments Per Kilobase of transcript per Million mapped reads. (C) GSEA of KEGG_Proteasome pathway between Group A (VQ-D1/D4) and Group B (VQ-D2/D5) myeloma cells. (D) Transcript levels of proteasome pathway genes Psmb6, Psmb7, and Psmb5, in CD138+ B220− cells from control and Group A and B VQ myeloma mice. These genes encode bortezomib-targeted β1, β2, and β5 subunit correspondingly. VQ donor of origin is color-coded as indicated. Results are presented as mean + SD. Two-sided t-Test was performed. (E, F) Btz dose-response curves in VQ MM 4935 (E) and 4938 (F) cell lines expressing shControl or shPsmb7. Results are presented as mean + SD. Two-sided t-Test was performed. (G, H) CD45.1 recipient mice were sub-lethally irradiated and injected with bone marrow cells from moribund VQ-D1 donor mouse or splenocytes from moribund VQ-D2 donor mouse. Six weeks (VQ-D1) or two weeks (VQ-D2) posttransplant, mice were treated with vehicle or bortezomib as described in Materials and Methods. (G) Serum protein electrophoresis was performed to quantify the γ-globulin/Albumin (G/A) ratios in VQ-D2 recipient mice at day 21 of treatment. Two-sided t-Test was performed. (H) Kaplan-Meier survival curves were plotted against days after treatment. Log-rank test was performed. Note: VQ-D1 results are taken from historical data [25]. FDR, false discovery rate; NES, normalized enrichment score; ns, not significant; p. adj., adjusted P-value. *, p <0.05; **, p <0.01; ***, p <0.001; ****, p <0.0001.