Purpose: Disturbed process of B-cell differentiation into plasmablasts (PBs)/plasma cells (PCs) is involved in multiple myeloma (MM). New strategies will be required to eliminate the MM cell clone for a long-term disease control. Because of its PB-like characteristics, the mus musculus myeloma SP 2/0 cell line was used in this study to search novel targets for PBs/PCs.
Methods/patients: Affymetrix microarrays and RNA-sequencing assays were used to search a novel different molecule (Gm6377) between PBs/PCs and mature B cells. Cell counting kit-8 (CCK8), flow cytometry (FACS), xenograft mouse model, and the luciferase reporter system were used to assess the effect of Gm6377 on SP 2/0 cell proliferation, cell cycle, tumor growth, and Myc promoter activation, respectively.
Results: We found that B cells expressed a high level of Gm6377 mRNA, whereas Gm6377 mRNA was decreased in PCs. In addition, SP 2/0 cells also expressed low levels of Gm6377 mRNA. Critically, Gm6377 overexpression suppressed SP 2/0 cell proliferation but not cell cycle. Furthermore, Gm6377 overexpression suppressed tumor progression in the SP 2/0 xenograft mouse model. Finally, we found that Gm6377 suppressed SP 2/0 cell proliferation by reducing the activation of the Myc promoter.
Conclusions: These results suggest that Gm6377 suppresses myeloma SP 2/0 cell growth by suppressing Myc. Thus, modulation of Gm6377 may be a potential therapeutic way to treat MM.
Keywords: B Cells; Gm6377; Multiple myeloma; Myc; Plasma cells.