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

J 2018

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

STEINER, Normann, Udo MULLER, Roman HÁJEK, Sabina ŠEVČÍKOVÁ, Bojana BORJAN et. al.

Basic information

Original name

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

Authors

STEINER, Normann (40 Austria, guarantor), Udo MULLER (40 Austria), Roman HÁJEK (203 Czech Republic), Sabina ŠEVČÍKOVÁ (203 Czech Republic, belonging to the institution), Bojana BORJAN (40 Austria), Karin JOHRER (40 Austria), Georg GOBEL (40 Austria), Andreas PIRCHER (40 Austria) and Eberhard GUNSILIUS (40 Austria)

Edition

Plos one, San Francisco, Public Library of Science, 2018, 1932-6203

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 2.776

RIV identification code

RIV/00216224:14110/18:00104193

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1371/journal.pone.0202045

UT WoS

000441308500045

Keywords in English

Multiple myeloma; monoclonal gammopathy of undetermined significance

Abstract

V originále

Introduction Multiple myeloma (MM), a malignant plasma cell disorder, is still an incurable disease. Thus, the identification of novel therapeutic targets is of utmost importance. Here, we evaluated the peripheral blood-based metabolic profile of patients with MM. Material & methods Peripheral blood plasma levels of 188 endogenous metabolites, including amino acids, biogenic amines, acylcarnitines, glycerophospholipids, sphingomyelins, and hexoses were determined in patients with plasma cell dyscrasias: monoclonal gammopathy of undetermined significance, a precursor stage of MM (MGUS, n = 15), newly diagnosed MM, (NDMM, n = 32), relapsed/refractory MM (RRMM, n = 19) and in 25 healthy controls by mass spectrometry. Results Patients with NDMM, RRMM and MGUS have a substantially different metabolomic profile than healthy controls. The amount of eight plasma metabolites significantly differs between the NDMM and MGUS group: free carnitine, acetylcarnitine, glutamate, asymmetric dimethylarginine (ADMA) and four phosphatidylcholine (PC) species. In addition, the levels of octadecanoylcarnitine, ADMA and six PCs were significantly different between RRMM and MGUS patients. 13 different concentrations of metabolites were found between RRMM and NDMM patients (free carnitine, acetyicarnitine, creatinine, five LysoPCs and PCs). Pathway analyses revealed a distinct metabolic profile with significant alterations in amino acid, lipid, and energy metabolism in healthy volunteers compared to MGUS/MM patients. Conclusion We identified different metabolic profiles in MGUS und MM patients in comparison to healthy controls. Thus, different metabolic processes, potentially the immunoregulation by indoleamine 2,3 dioxygenase-1 (IDO), which is involved in cancer development and progression supporting inflammatory processes in the tumor microenvironment and glutaminolysis, can serve as novel promising therapeutic targets in MM.

Citovat

STEINER, Normann, Udo MULLER, Roman HÁJEK, Sabina ŠEVČÍKOVÁ, Bojana BORJAN, Karin JOHRER, Georg GOBEL, Andreas PIRCHER and Eberhard GUNSILIUS. The metabolomic plasma profile of myeloma patients is considerably different from healthy subjects and reveals potential new therapeutic targets. Plos one. San Francisco: Public Library of Science, 2018, vol. 13, No 8, p. 1-13. ISSN 1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0202045.

@article{1455216,
   author = {Steiner, Normann and Muller, Udo and Hájek, Roman and Ševčíková, Sabina and Borjan, Bojana and Johrer, Karin and Gobel, Georg and Pircher, Andreas and Gunsilius, Eberhard},
   article_location = {San Francisco},
   article_number = {8},
   doi = {http://dx.doi.org/10.1371/journal.pone.0202045},
   keywords = {Multiple myeloma; monoclonal gammopathy of undetermined significance},
   language = {eng},
   issn = {1932-6203},
   journal = {Plos one},
   title = {The metabolomic plasma profile of myeloma patients is considerably different from healthy subjects and reveals potential new therapeutic targets},
   volume = {13},
   year = {2018}
}

TY  - JOUR
ID  - 1455216
AU  - Steiner, Normann - Muller, Udo - Hájek, Roman - Ševčíková, Sabina - Borjan, Bojana - Johrer, Karin - Gobel, Georg - Pircher, Andreas - Gunsilius, Eberhard
PY  - 2018
TI  - The metabolomic plasma profile of myeloma patients is considerably different from healthy subjects and reveals potential new therapeutic targets
JF  - Plos one
VL  - 13
IS  - 8
SP  - 1-13
EP  - 1-13
PB  - Public Library of Science
SN  - 19326203
KW  - Multiple myeloma
KW  - monoclonal gammopathy of undetermined significance
N2  - Introduction Multiple myeloma (MM), a malignant plasma cell disorder, is still an incurable disease. Thus, the identification of novel therapeutic targets is of utmost importance. Here, we evaluated the peripheral blood-based metabolic profile of patients with MM. Material & methods Peripheral blood plasma levels of 188 endogenous metabolites, including amino acids, biogenic amines, acylcarnitines, glycerophospholipids, sphingomyelins, and hexoses were determined in patients with plasma cell dyscrasias: monoclonal gammopathy of undetermined significance, a precursor stage of MM (MGUS, n = 15), newly diagnosed MM, (NDMM, n = 32), relapsed/refractory MM (RRMM, n = 19) and in 25 healthy controls by mass spectrometry. Results Patients with NDMM, RRMM and MGUS have a substantially different metabolomic profile than healthy controls. The amount of eight plasma metabolites significantly differs between the NDMM and MGUS group: free carnitine, acetylcarnitine, glutamate, asymmetric dimethylarginine (ADMA) and four phosphatidylcholine (PC) species. In addition, the levels of octadecanoylcarnitine, ADMA and six PCs were significantly different between RRMM and MGUS patients. 13 different concentrations of metabolites were found between RRMM and NDMM patients (free carnitine, acetyicarnitine, creatinine, five LysoPCs and PCs). Pathway analyses revealed a distinct metabolic profile with significant alterations in amino acid, lipid, and energy metabolism in healthy volunteers compared to MGUS/MM patients. Conclusion We identified different metabolic profiles in MGUS und MM patients in comparison to healthy controls. Thus, different metabolic processes, potentially the immunoregulation by indoleamine 2,3 dioxygenase-1 (IDO), which is involved in cancer development and progression supporting inflammatory processes in the tumor microenvironment and glutaminolysis, can serve as novel promising therapeutic targets in MM.
ER  -

STEINER, Normann, Udo MULLER, Roman HÁJEK, Sabina ŠEVČÍKOVÁ, Bojana BORJAN, Karin JOHRER, Georg GOBEL, Andreas PIRCHER and Eberhard GUNSILIUS. The metabolomic plasma profile of myeloma patients is considerably different from healthy subjects and reveals potential new therapeutic targets. \textit{Plos one}. San Francisco: Public Library of Science, 2018, vol.~13, No~8, p.~1-13. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0202045.

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