![]() Finally, we examine MM-induced alterations of metabolites and their therapeutic potential for the treatment of MM. We perform a metabolomic analysis of BM liquid and peripheral blood (PB) plasma-derived from MM patients and healthy donors (HDs). In this work, we attempt to fill the gap in our knowledge of metabolites involved in MM. The function of metabolites in MM progression is even more poorly understood. However, a detailed understanding of the metabolite profile in the MM BM microenvironment is still lacking. reported that blocking fructose utilization attenuates proliferation and drug resistance in acute myeloid leukemia 12. found that a panel of five plasma metabolites can serve as a noninvasive diagnostic marker for pancreatic cancer 11, and Chen et al. Recently, it has been shown that tumor-associated metabolites can potentially be used for clinical diagnosis and therapy in cancer. Tumor initiation results in metabolite alterations in the tumor microenvironment which, in turn, contribute to tumor progression 7, 8, 9, 10. The metabolic profile is strongly influenced by pathological changes. More recently, we demonstrated that intestinal bacteria promote MM progression by elevating the level of BM glutamine in MM 6, indicating that the alterations of metabolite levels in the BM microenvironment can affect MM. Metabolic reprogramming in the tumor microenvironment reportedly promotes tumor progression in various types of cancer 3, 4, 5. Recent findings from our group and others have shown that genetic variations and the BM microenvironment contribute to malignant progression and anti-cancer therapy resistance in MM 1, 2. Multiple myeloma (MM) is characterized by transformed clonal plasma cells in the bone marrow (BM) microenvironment and monoclonal immunoglobulin accumulation in the blood or urine 1. Together, we identify glycine as a key metabolic regulator of MM, unveil molecular mechanisms governing MM progression, and provide a promising therapeutic strategy for MM treatment. Inhibiting glycine utilization via SLC6A9 knockdown or the treatment with betaine suppresses MM cell proliferation and enhances the effects of bortezomib on MM cells. MM cells utilize the channel protein solute carrier family 6 member 9 (SLC6A9) to absorb extrinsic glycine subsequently involved in the synthesis of glutathione (GSH) and purines. Here, we show that the glycine concentration in the BM microenvironment is elevated due to bone collagen degradation mediated by MM cell-secreted matrix metallopeptidase 13 (MMP13), while the elevated glycine level is linked to MM progression. However, the lack of knowledge about the metabolic profile in the bone marrow (BM) microenvironment of multiple myeloma (MM) limits our understanding of MM progression. Metabolites in the tumor microenvironment are a critical factor for tumor progression.
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