Pb2073: evaluation of the plasma metabolomic profile of mgus and multiple myeloma patients

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Multiple myeloma (MM) is a one of hematological malignancy of antibody-producing plasma cells. Its development is preceded by a premalignant condition defined as monoclonal gammopathy of undetermined significance (MGUS). This precursor state is asymptomatic and its presence does not always determine the onset of the disease. The clinical course of MM varies considerably, and despite to introduction of plenty of very effective new drugs, the disease is still considered incurable. Metabolomics, a relatively new field of science, may assess the complete set of metabolites or small molecule chemicals that may be involved in biological processes occurring in neoplastic cells. Aims: The aim of the study was to determine the metabolic profiles of MGUS and multiple myeloma patients. An additional objective was to identify potential biomarkers of MGUS progression to MM. Methods: A total of 100 people participated in the study. The study group consisted of patients with newly diagnosed MGUS (n=30) and multiple myeloma (n=50) at various stages of the disease during the collection of the material. Both groups were similar in terms of median age. The control was a group of healthy people matched in terms of sex and age (n=20). The study design was to obtain a venous blood sample from fasting patients during routine morning diagnostic examinations. The obtained material (plasma), after initial processing, was evaluated using a liquid chromatograph coupled with a sensitive mass detector (LC-QTOF-MS) using a non-targeted analysis method (metabolomic fingerprinting). Results: After initial data processing by LC-MS, 751 metabolic features were obtained. Taking into account the experimental weight and obtained fragmentation spectra and comparing them to the molecular weights and reference spectra in Internet databases it was possible to identify 104 compounds that differentiated metabolomic profiles of patients in particular groups. In the MGUS group, compared to the control group, an increase in the level of identified compounds from the group of carnitines and sphingomyelins (SM) and compounds such as bilirubin, carboxy-methyl-propyl-furanopropanoic acid, benzothiazolethion and piperine was observed. Compared to the control group, in the group of patients with MM, an increase in the level of carnitines, phosphatidylethanolamines (PE) and compounds such as bilirubin, carboxy-methyl-propyl-furanopropanoic acid and benzothiazolethion was observed. In both groups (MGUS and MM) when compared with healthy study participants decreased levels of lysophosphatidylinositols (LPI), eicosapentaenoic acid (EPA), arachidonic acid and an inconclusive trend of changes in the levels of phosphatidylcholines (PC), lysophostatidylcholines (LPC) and lysophosphatidylethanolamines (LPE) were observed. Additionally, unlike MGUS vs. control group, in the MM group there was a decrease in the level of SM. In the last comparison (MM vs. MGUS), a decrease in the level of carnitines, SM, LPI, LPC, PC, PE, bilirubin and EPA was found - the exceptions were PC (34:3), PE (16:0/18:2), LPE (16:0), the level of which increased among patients with MM compared to the MGUS group. Summary/Conclusion: The study allowed to determine significant differences in metabolomic profiles of the study groups. The observed changes in the level of identified metabolites may by associated with changes in the cellular metabolism of clonal plasma cells, for example with increased energy demand, synthesis of cell membranes, activation of enzymes and production of pro-cancer metabolites. All of these may be involved in carcinogenesis and the obtained information may be useful in determine a new targets for MM therapy. Keywords: Multiple myeloma, MGUS