Metabolomic and Lipidomic Profiling of Bone Marrow Plasma Differentiates Patients with Monoclonal Gammopathy of Undetermined Significance from Multiple Myeloma.

Autor: Gonsalves WI; The Division of Hematology, Mayo Clinic, Rochester, MN, United States. gonsalves.wilson@mayo.edu., Broniowska K; Metabolon Inc, Morrisville, NC, Mayo Clinic, Rochester, MN, United States., Jessen E; Biostatistics and Informatics, Mayo Clinic, Rochester, MN, United States., Petterson XM; Endocrinology and the Department of Oncology, Mayo Clinic, Rochester, MN, United States., Bush AG; Endocrinology and the Department of Oncology, Mayo Clinic, Rochester, MN, United States., Gransee J; Endocrinology and the Department of Oncology, Mayo Clinic, Rochester, MN, United States., Lacy MQ; The Division of Hematology, Mayo Clinic, Rochester, MN, United States., Hitosugi T; Molecular Therapeutics, Mayo Clinic, Rochester, MN, United States., Kumar SK; The Division of Hematology, Mayo Clinic, Rochester, MN, United States.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Jun 24; Vol. 10 (1), pp. 10250. Date of Electronic Publication: 2020 Jun 24.
DOI: 10.1038/s41598-020-67105-3
Abstrakt: Oncogenic drivers of progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) such as c-MYC have downstream effects on intracellular metabolic pathways of clonal plasma cells (PCs). Thus, extracellular environments such as the bone marrow (BM) plasma likely have unique metabolite profiles that differ from patients with MGUS compared to MM. This study utilized an untargeted metabolite and targeted complex lipid profiling of BM plasma to identify significant differences in the relative metabolite levels between patients with MGUS and MM from an exploratory cohort. This was followed by verification of some of the metabolite differences of interest by targeted quantification of the metabolites using isotopic internal standards in the exploratory cohort as well as an independent validation cohort. Significant differences were noted in the amino acid profiles such as decreased branch chain amino acids (BCAAs) and increased catabolism of tryptophan to the active kynurenine metabolite 3-hydroxy-kynurenine between patients with MGUS and MM. A decrease in the total levels of complex lipids such as phosphatidylethanolamines (PE), lactosylceramides (LCER) and phosphatidylinositols (PI) were also detected in the BM plasma samples from MM compared to MGUS patients. Thus, metabolite and complex lipid profiling of the BM plasma identifies differences in levels of metabolites and lipids between patients with MGUS and MM. This may provide insight into the possible differences of the intracellular metabolic pathways of their clonal PCs.
Databáze: MEDLINE
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