Increasing Wnt signaling in the bone microenvironment reduces myeloma tumor burden in bone. Mice were inoculated intravenously with 5TGM1-pcDNA or 5TGM1-ΔNTCF4 myeloma cells that homed to bone marrow and spleen. Single cell suspensions were isolated from bone marrow and spleen, and the proportion of GFP-positive cells was determined by flow cytometry. LiCl significantly reduced the proportion of GFP-positive cells in the bone marrow of both 5TGM1-pcDNA and 5TGM1-ΔNTCF4 myeloma–bearing mice (A). In contrast, LiCl significantly increased the proportion of GFP-positive bone marrow cells in the spleen of 5TGM1-pcDNA myeloma–bearing mice but not 5TGM1-ΔNTCF4 myeloma–bearing mice (B). Treatment with LiCl significantly reduced serum IgG_2bκ concentrations in both 5TGM1-pcDNA and 5TGM1-ΔNTCF4 myeloma–bearing mice (C). Data are expressed as means (± SEM). *P < .05 compared with control. **P < .01 compared with nontumor. †P < .05, ††P < .01 compared with untreated.