The metabolomic plasma profile of myeloma patients is considerably different from healthy subjects and reveals potential new therapeutic targets

Steiner, Normann; Müller, Udo; Ševčı́ková, Sabina; Borjan, Bojana; Jöhrer, Karin; Göbel, Georg; Pircher, Andreas; Gunsilius, Eberhard

doi:10.1371/journal.pone.0202045

Cited by 42 publications

(45 citation statements)

References 38 publications

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“…In targeted metabolomics, data cleaning was performed with reference to the criteria used in previous studies [ 32 , 33 ]. Values greater than the limit of detection (LOD) in the raw data of each group were chosen for (semi-) quantification.…”

Section: Methodsmentioning

confidence: 99%

Revealing Metabolic Perturbation Following Heavy Methamphetamine Abuse by Human Hair Metabolomics and Network Analysis

Kim

Jang

et al. 2020

IJMS

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Methamphetamine (MA) is a highly addictive central nervous system stimulant. Drug addiction is not a static condition but rather a chronically relapsing disorder. Hair is a valuable and stable specimen for chronic toxicological monitoring as it retains toxicants and metabolites. The primary focus of this study was to discover the metabolic effects encompassing diverse pathological symptoms of MA addiction. Therefore, metabolic alterations were investigated in human hair following heavy MA abuse using both targeted and untargeted mass spectrometry and through integrated network analysis. The statistical analyses (t-test, variable importance on projection score, and receiver-operator characteristic curve) demonstrated that 32 metabolites (in targeted metabolomics) as well as 417 and 224 ion features (in positive and negative ionization modes of untargeted metabolomics, respectively) were critically dysregulated. The network analysis showed that the biosynthesis or metabolism of lipids, such as glycosphingolipids, sphingolipids, glycerophospholipids, and ether lipids, as well as the metabolism of amino acids (glycine, serine and threonine; cysteine and methionine) is affected by heavy MA abuse. These findings reveal crucial metabolic effects caused by MA addiction, with emphasis on the value of human hair as a diagnostic specimen for determining drug addiction, and will aid in identifying robust diagnostic markers and therapeutic targets.

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Section: Methodsmentioning

confidence: 99%

Revealing Metabolic Perturbation Following Heavy Methamphetamine Abuse by Human Hair Metabolomics and Network Analysis

Kim

Jang

et al. 2020

IJMS

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“…Decreased PC was previously observed in MM cells compared to normal plasma cells [8]. Recently, Steiner et al reported significantly lower circulating plasma levels of several PCs, and elevated lyso-PCs in RRMM compared to NDMM [27]. Hydrolysis of PCs by phospholipases generate lyso-PCs and a free fatty acid which could be further processed to generate lipid second messengers such as arachidonic acid, prostaglandins and leukotrienes [28].…”

Section: Discussionmentioning

confidence: 96%

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

et al. 2020

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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.

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“…Recently, Steiner et al . reported significantly lower circulating plasma levels of several PCs, and elevated lyso-PCs in RRMM compared to NDMM [27]. Hydrolysis of PCs by phospholipases generate lyso-PCs and a free fatty acid which could be further processed to generate lipid second messengers such as arachidonic acid, prostaglandins and leukotrienes [28].…”

Section: Discussionmentioning

confidence: 99%

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

Mohamed

Collins

Jiang

et al. 2019

Preprint

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17Background: Multiple myeloma (MM) is a hematological malignancy characterized by the 18 clonal expansion of malignant plasma cells. Though durable remissions are possible, MM is 19 considered incurable, with relapse occurring in almost all patients. There has been limited 20 data reported on the lipid metabolism changes in plasma cells during MM progression. Here, 21we evaluated the feasibility of concurrent lipidomics and proteomics analyses from patient 22 plasma cells, and report these data on a limited number of patient samples, demonstrating the 23 feasibility of the method, and establishing hypotheses to be evaluated in the future. 24Methods: Plasma cells were purified from fresh bone marrow aspirates using CD138 25 microbeads. Proteins and lipids were extracted using a bi-phasic solvent system with 26 methanol, methyl tert-butyl ether, and water. Untargeted proteomics, untargeted and targeted 27 lipidomics were performed on 7 patient samples using liquid chromatography-mass 28 spectrometry. Two comparisons were conducted: high versus low risk; relapse versus newly 29 diagnosed. Proteins and pathways enriched in the relapsed group was compared to a public 30 transcriptomic dataset from Multiple Myeloma Research Consortium reference collection 31 (n=222) at gene and pathways level. 32Results: From one million purified plasma cells, we were able to extract material and 33 complete untargeted (~6000 and ~3600 features in positive and negative mode respectively) 34 and targeted lipidomics (313 lipids), as well as untargeted proteomics analysis (~4100 35 reviewed proteins). Comparative analyses revealed limited differences between high and low 36 risk groups (according to the standard clinical criteria), hence we focused on drawing 37 comparisons between the relapsed and newly diagnosed patients. Untargeted and targeted 38 lipidomics indicated significant down-regulation of phosphatidylcholines (PCs) in relapsed 39 MM. Although there was limited overlap of the differential proteins/transcripts, 76 40 Page 3 of 29 significantly enriched pathways in relapsed MM were common between proteomics and 41 transcriptomics data. Further evaluation of transcriptomics data for lipid metabolism network 42 revealed enriched correlation of PC, ceramide, cardiolipin, arachidonic acid and cholesterol 43 metabolism pathways to be exclusively correlated among relapsed but not in newly-44 diagnosed patients. 45 Conclusions:This study establishes the feasibility and workflow to conduct integrated 46 lipidomics and proteomics analyses on patient-derived plasma cells. Potential lipid 47 metabolism changes associated with MM relapse warrant further investigation. 48

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The metabolomic plasma profile of myeloma patients is considerably different from healthy subjects and reveals potential new therapeutic targets

Cited by 42 publications

References 38 publications

Revealing Metabolic Perturbation Following Heavy Methamphetamine Abuse by Human Hair Metabolomics and Network Analysis

Revealing Metabolic Perturbation Following Heavy Methamphetamine Abuse by Human Hair Metabolomics and Network Analysis

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

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

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