Background: Tumor-associated macrophages (TAMs) are originated from circulating mononuclear cells in peripheral blood. They result from the recruitment of tumor cells and are a vital constituent of the tumor microenvironment. TAMs may be involved in the immunological escape of vicious clonal plasma cells (PC) in the bone marrow (BM) of sufferers with myeloma.Methods: From March 2020 to January 2021, 28 healthy controls (HC) and 86 multiple myeloma (MM) (53 newly diagnosed MM [NDMM] and 33 remissions) patients were enrolled as objects of the study. The expression of TAMs in the BM, CSF1 on CD138 + cells, and CSF1R on macrophages were detected by the method of flow cytometry, and the expression of PD-1 on CD8 + T cells and PD-L1 on TAMs were also done. Bone marrow mononuclear cells (BMMNCs) were extracted and cultured into TAMs, CD8 + T cells were sorted by magnetic beads and cultured, a coculture system was established and different inhibitors were added.The expression of the perforin and granzyme B was detected by flow cytometry. Results:The percentage of TAMs in NDMM group (61.49 ± 2.176%) increased when compared with remission (23.08 ± 1.699%, p < 0.001) and HC group (17.95 ± 1.865%, p < 0.001), and TAMs decreased after adding CSF1R inhibitor.Moreover, the expression of CSF1 on CD138 + cells increased significantly in NDMM group (17.090 ± 0.9156%) than remission (8.214 ± 0.5911% p < 0.001), and HC group (5.257 ± 0.6231%, p < 0.001), and CSF1R on macrophages increased significantly in NDMM group (58.78 ± 2.286%) than remission (20.74 ± 1.376%, p < 0.001) and HC group (17.42 ± 1.081%, p < 0.001). The expression of PD-1 on CD8 + T cells in NDMM group (32.64 ± 2.982%) increased than remission (20.35 ± 2.335% p < 0.01) and HC group (17.53 ± 1.349%, p < 0.001), and PD-L1 on TAMs also increased in NDMM group (50.92 ± 2.554%) than remission (20.02 ± 1.893%, p < 0.001) and HC group (13.08 ± 1.289%, p < 0.001). When

Pim-2 kinase is overexpressed in multiple myeloma (MM) and is associated with poor prognosis in patients with MM. Changes in quantitative metabolism, glycolysis, and oxidative phosphorylation pathways are reportedly markers of all tumor cells. However, the relationship between Pim-2 and glycolysis in MM cells remains unclear. In the present study, we explored the relationship between Pim-2 and glycolysis. We found that Pim-2 inhibitors inhibited glycolysis and energy production in MM cells. Inhibition of Pim-2 decreased the proliferation of MM tumor cells and increased their susceptibility to apoptosis. Our data suggest that reduced Pim-2 expression inhibits the energy metabolism process in MM, thereby inhibiting tumor progression. Hence, Pim-2 is a potential metabolic target for MM treatment.

The suppression of osteoblast (OB) activity is partially responsible for multiple myeloma (MM) bone disease. Long non-coding RNAs (lncRNAs) play a vital role in bone formation and resorption. However, their functions in OBs from patients with MM have rarely been reported. Through high-throughput sequencing of OBs from patients with MM and healthy controls, we identified several lncRNAs and messenger RNAs (mRNAs) with different expression profile and validated them using quantitative real-time PCR. In total, 22 upregulated and 21 downregulated lncRNAs were found in OBs from patients with MM. Moreover, 18 upregulated protein-coding mRNAs were identified. The expression levels of LINC01473 and its associated co-expression mRNA, CD74, were higher in patients with MM than in healthy controls (p=0.047 and p=0.016, respectively). LINC01473 expression demonstrated a negative correlation with serum interleukin-2 and tumor necrosis factor α levels, whereas the expression of mRNA CD74 was positively associated with serum lactic dehydrogenase in patients with MM. Aberrant expression of lncRNAs and mRNAs was observed in OBs from patients with MM. This study identifies new promising targets for further research on imbalanced bone formation and resorption and MM immune escape.

The persistence of tumor load in multiple myeloma (MM) lead to relapse in patients achieving complete remission (CR). Appropriate and effective methods of myeloma tumor load monitoring are important for guiding clinical management. This study aimed to clarify the value of microvesicles in monitoring MM tumor load. Microvesicles in bone marrow and peripheral blood were isolated by differential ultracentrifugation and detected by flow cytometry. Western blotting was applied to assess myosin light chain phosphorylation levels. Flow cytometry to detect Ps+CD41a−, Ps+CD41a−CD138+, Ps+CD41a−BCMA+ microvesicles from bone marrow can be used to predict myeloma burden, furthermore, Ps+CD41a− microvesicles may as a potential index to MRD test. Mechanistically, the releasing of microvesicles from MM cell was regulated by Pim-2 Kinase via Phosphorylation of MLC-2 protein.

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