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

Autor(es)

Cotrim Guerreiro da Silva, Ismael Dale ^[1] ; de Castro Levatti, Erica Valadares ^[2] ; Pedroso, Amanda Paula ^[3] ; Lobo Marchioni, Dirce Maria ^[4] ; Ferreira Carioca, Antonio Augusto ^{[4, 5]} ; Braga Colleoni, Gisele Wally ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Paulista Sch Med, Dept Gynecol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Paulista Sch Med, Dept Clin & Expt Oncol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Paulista Sch Med, Dept Physiol, Sao Paulo - Brazil

^[4] Univ Sao Paulo MUSP, Sch Publ Hlth, Nutr Dept, Sao Paulo - Brazil

^[5] Univ Fortaleza UNIFOR, Nutr Dept, Fortaleza, Ceara - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 DEC 14 2020.
• Citações Web of Science: 0

Resumo

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 beta 2-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. (AU)

• Processo FAPESP: 17/21801-2 - Preditores de gravidade e novos tratamentos para neoplasias da medula óssea
• Beneficiário: Sara Teresinha Olalla Saad
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/17668-6 - Identificação de marcadores tumorais e possíveis alvos terapêuticos em doenças linfoproliferativas de células B
• Beneficiário: Gisele Wally Braga Colleoni
• Modalidade de apoio: Auxílio à Pesquisa - Temático