Mass spectrometry-based lipidomics identifies select triacylglycerol species as differentially abundant in the bone marrow microenvironment of patients with multiple myeloma compared to monoclonal gammopathy of unknown significance

Introduction: Alterations in the bone marrow (BM) tumor microenvironment (TME) are closely associated with the progression of premalignant clonal plasma cells in monoclonal gammopathy of undetermined significance (MGUS) to malignant clonal plasma cells in multiple myeloma (MM), though the extent to which these alterations are causative remains unclear. Whether lipidomic changes are part of the BM TME alterations associated with this disease progression remains poorly understood. Objectives: To investigate and compare the levels of individual lipid species across different lipid classes in the BM-TME, specifically BM plasma, of MGUS and MM patients. Methods: A mass spectrometry-based targeted lipidomics approach was employed to quantify individual lipid species from various lipid classes in BM plasma samples obtained from 22 MGUS and 24 MM patients. Results: Significant differences in lipid species were observed between the BM-TME of MGUS and MM patients. MM patients exhibited elevated levels of triacylglycerol (TAG) species containing long-chain fatty acids (FAs) with higher degrees of unsaturation. In contrast, MGUS patients had higher levels of TAG species with shorter-chain FAs and lower unsaturation. Additionally, MM patients with a higher percentage of clonal plasma cells and increased proliferation rates displayed lipid profiles more closely resembling MM-associated signatures than MGUS. Conclusion: The differential abundance of individual lipid species within the BM-TME highlights metabolic changes associated with the progression from MGUS to MM. These findings provide valuable insights into the lipidomic underpinnings of MM pathogenesis, offering a foundation for future research into metabolic biomarkers and therapeutic targets.