Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease

Abstract The aim of this study was to identify novel plasma metabolic signatures with possible relevance during multiple myeloma (MM) development and progression. A biochemical quantitative phenotyping platform based on targeted electrospray ionization tandem mass spectrometry technology was used to...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ismael Dale Cotrim Guerreiro da Silva, Erica Valadares de Castro Levatti, Amanda Paula Pedroso, Dirce Maria Lobo Marchioni, Antonio Augusto Ferreira Carioca, Gisele Wally Braga Colleoni
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/85370f2e321f4764a8a70a8f150fa851
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:85370f2e321f4764a8a70a8f150fa851
record_format	dspace
spelling	oai:doaj.org-article:85370f2e321f4764a8a70a8f150fa8512021-12-02T13:58:37ZBiochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease10.1038/s41598-020-75862-42045-2322https://doaj.org/article/85370f2e321f4764a8a70a8f150fa8512020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-75862-4https://doaj.org/toc/2045-2322Abstract The aim of this study was to identify novel plasma metabolic signatures with possible relevance during multiple myeloma (MM) development and progression. A biochemical quantitative phenotyping platform based on targeted electrospray ionization tandem mass spectrometry technology was used to aid in the identification of any eventual perturbed biochemical pathway in peripheral blood plasma from 36 MM patients and 73 healthy controls. Our results showed that MM cases present an increase in short and medium/long-chain species of acylcarnitines resembling Multiple AcylCoA Dehydrogenase Deficiency (MADD), particularly, associated with MM advanced International Staging System (ISS). Lipids profile showed lower concentrations of phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelins (SM) in the MM patients and its respective ISS groups. MM cases were accompanied by a drop in the concentration of essential amino acids, especially tryptophan, with a significant inverse correlation between the progressive drop in tryptophan with the elevation of β2-microglobulin, with the increase in systemic methylation levels (Symmetric Arginine Dimethylation, SDMA) and with the accumulation of esterified carnitines in relation to free carnitine (AcylC/C0). Serotonin was significantly elevated in cases of MM, without a clear association with ISS. Kynurenine/tryptophan ratio demonstrates that the activity of dioxigenases is even higher in the cases classified as ISS 3. In conclusion, our study showed that MM patients at diagnosis showed metabolic disorders resembling both mitochondrial complexes I and II and Hartnup-like disturbances as underlying conditions, also influencing different stages of the disease.Ismael Dale Cotrim Guerreiro da SilvaErica Valadares de Castro LevattiAmanda Paula PedrosoDirce Maria Lobo MarchioniAntonio Augusto Ferreira CariocaGisele Wally Braga ColleoniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ismael Dale Cotrim Guerreiro da Silva Erica Valadares de Castro Levatti Amanda Paula Pedroso Dirce Maria Lobo Marchioni Antonio Augusto Ferreira Carioca Gisele Wally Braga Colleoni Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease
description	Abstract The aim of this study was to identify novel plasma metabolic signatures with possible relevance during multiple myeloma (MM) development and progression. A biochemical quantitative phenotyping platform based on targeted electrospray ionization tandem mass spectrometry technology was used to aid in the identification of any eventual perturbed biochemical pathway in peripheral blood plasma from 36 MM patients and 73 healthy controls. Our results showed that MM cases present an increase in short and medium/long-chain species of acylcarnitines resembling Multiple AcylCoA Dehydrogenase Deficiency (MADD), particularly, associated with MM advanced International Staging System (ISS). Lipids profile showed lower concentrations of phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelins (SM) in the MM patients and its respective ISS groups. MM cases were accompanied by a drop in the concentration of essential amino acids, especially tryptophan, with a significant inverse correlation between the progressive drop in tryptophan with the elevation of β2-microglobulin, with the increase in systemic methylation levels (Symmetric Arginine Dimethylation, SDMA) and with the accumulation of esterified carnitines in relation to free carnitine (AcylC/C0). Serotonin was significantly elevated in cases of MM, without a clear association with ISS. Kynurenine/tryptophan ratio demonstrates that the activity of dioxigenases is even higher in the cases classified as ISS 3. In conclusion, our study showed that MM patients at diagnosis showed metabolic disorders resembling both mitochondrial complexes I and II and Hartnup-like disturbances as underlying conditions, also influencing different stages of the disease.
format	article
author	Ismael Dale Cotrim Guerreiro da Silva Erica Valadares de Castro Levatti Amanda Paula Pedroso Dirce Maria Lobo Marchioni Antonio Augusto Ferreira Carioca Gisele Wally Braga Colleoni
author_facet	Ismael Dale Cotrim Guerreiro da Silva Erica Valadares de Castro Levatti Amanda Paula Pedroso Dirce Maria Lobo Marchioni Antonio Augusto Ferreira Carioca Gisele Wally Braga Colleoni
author_sort	Ismael Dale Cotrim Guerreiro da Silva
title	Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease
title_short	Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease
title_full	Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease
title_fullStr	Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease
title_full_unstemmed	Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease
title_sort	biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes i and ii and a hartnup-like disturbance as underlying conditions, also influencing different stages of the disease
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/85370f2e321f4764a8a70a8f150fa851
work_keys_str_mv	AT ismaeldalecotrimguerreirodasilva biochemicalphenotypingofmultiplemyelomapatientsatdiagnosisrevealsadisorderofmitochondrialcomplexesiandiiandahartnuplikedisturbanceasunderlyingconditionsalsoinfluencingdifferentstagesofthedisease AT ericavaladaresdecastrolevatti biochemicalphenotypingofmultiplemyelomapatientsatdiagnosisrevealsadisorderofmitochondrialcomplexesiandiiandahartnuplikedisturbanceasunderlyingconditionsalsoinfluencingdifferentstagesofthedisease AT amandapaulapedroso biochemicalphenotypingofmultiplemyelomapatientsatdiagnosisrevealsadisorderofmitochondrialcomplexesiandiiandahartnuplikedisturbanceasunderlyingconditionsalsoinfluencingdifferentstagesofthedisease AT dircemarialobomarchioni biochemicalphenotypingofmultiplemyelomapatientsatdiagnosisrevealsadisorderofmitochondrialcomplexesiandiiandahartnuplikedisturbanceasunderlyingconditionsalsoinfluencingdifferentstagesofthedisease AT antonioaugustoferreiracarioca biochemicalphenotypingofmultiplemyelomapatientsatdiagnosisrevealsadisorderofmitochondrialcomplexesiandiiandahartnuplikedisturbanceasunderlyingconditionsalsoinfluencingdifferentstagesofthedisease AT giselewallybragacolleoni biochemicalphenotypingofmultiplemyelomapatientsatdiagnosisrevealsadisorderofmitochondrialcomplexesiandiiandahartnuplikedisturbanceasunderlyingconditionsalsoinfluencingdifferentstagesofthedisease
_version_	1718392210358009856

Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease

Ejemplares similares