Objective:Recent researches suggested that the abnormalities of bone marrow microenvironment have important implications for the genesis and evolution of multiple myeloma. However,the gene expression profile (GEP)changes in the interaction between bone marrow mesenchymal stem cell(MSC) and myeloma cells are not reported. Methods:To investigate the pathogenesis of multiple myeloma,cDNA microarray was employed to investigate the GEP of MSC before and after interacting with myeloma cells. And the genes with differential expression MSC co-cultured with myeloma cells (the MC groups)or cultured alone to continue after the removal of MM cells (MA groups)compared with the control groups (the MK groups)were screened by scanning and analyzed by computer software. Results:After co-cultured of MSC with MM cells (the MC groups),among total 10 000 genes,we filtered a total of 837 differential representing genes (837/10 000,8.37%),of which there were 472 up-regulated genes (472/837,56.39%)and 365 genes were down-regulated(365/837,43.61%). We found 367 differentially expressed genes in the MA groups compared to the control ones,including 218 up-regulated genes (218/367,59.40%)and 149 down-regulated genes(149/367,40.60%). Then we selected eight genes(MMP-1,FGFR2,ANGPTL4,MFAP5,TGM2,STC1,CCL7 and IL-32)from differential genes to verify by real-time quantitative PCR and their functions were explored. The Real-time quantitative PCR results were consistent with cDNA microarray results. Conclusion: It is indicated that myeloma cells induce a variety of gene expression changes of normal bone marrow MSC,and some changes still exist even after the removal of MM cells. In addition,among the eight selected genes in this study,seven of them have not been reported to be involved in the pathogenesis of multiple myeloma.