Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome

Abstract

Background Multiple myeloma (MM) is a hematological malignancy characterized by the clonal expansion of malignant plasma cells. Though durable remissions are possible, MM is considered incurable, with relapse occurring in almost all patients. There has been limited data reported on the lipid metabolism changes in plasma cells during MM progression. Here, we evaluated the feasibility of concurrent lipidomics and proteomics analyses from patient plasma cells, and report these data on a limited number of patient samples, demonstrating the feasibility of the method, and establishing hypotheses to be evaluated in the future. Methods Plasma cells were purified from fresh bone marrow aspirates using CD138 microbeads. Proteins and lipids were extracted using a bi-phasic solvent system with methanol, methyl tertbutyl ether, and water. Untargeted proteomics, untargeted and targeted lipidomics were performed on 7 patient samples using liquid chromatography-mass spectrometry. Two comparisons were conducted: high versus low risk; relapse versus newly diagnosed. Proteins and pathways enriched in the relapsed group was compared to a public transcriptomic dataset from Multiple Myeloma Research Consortium reference collection (n = 222) at gene and pathways level.

Sequential Precipitation and Delipidation Enables Efficient Enrichment of Low-Molecular Weight Proteins and Peptides from Human Plasma

“…In addition, we think SPD could also facilitate the top-down analysis of intact LMW proteins in plasma and be used for concurrent lipidomics and peptidomics . Taken together, the SPD method will be of high interest to the field of clinical proteomics and could greatly accelerate the discovery rate of potential biomarkers and drug targets.…”

Metabolism in the Tumour-Bone Microenvironment

“…The frequency with which bone marrow aspirates are taken during myeloma diagnosis and disease progression lends itself well to analyses such as metabolomics and lipidomics, with a number of studies demonstrating changes in the metabolic profiles of myeloma cells isolated from patients with multiple myeloma. One such study performed concurrent lipidomics and proteomics in myeloma cells isolated from newly diagnosed and relapsed patients, revealing a downregulation of phosphatidylcholines in relapsed myeloma [35]. Gonsalves et al combined untargeted metabolite and targeted lipid profiling of bone marrow plasma from patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS), revealing changes in amino acid profiles and a reduction in complex lipids in patients with myeloma, as compared to MGUS [36].…”

Choline PET/CT in Multiple Myeloma

“…Fatty acid synthetase expression is also upregulated in myeloma cells, contributing to proliferation and survival [16]. In relapsed and in high-risk MM, phosphatidylcholine is downregulated and is thought to be hydrolyzed to form lipid messengers, responsible for tumor dissemination [17,18]. Hence, MM cells may exhibit different patterns of uptake depending on the patient's previous exposure to MM drugs.…”