ECTS2013 Poster Presentations Cancer and bone: basic, translational and clinical (31 abstracts)
Metabolomics identifies plasma biomarkers of multiple myeloma development and progression
Elisabetta Mariani 1, , Francesca Fontana 1, , Silvia Mari 3 , Jose Manuel Garcia Manteiga 1, , Magda Marcatti 4 , Nicola Napoli 1, , Francesco Camnasio 6 , Gianfranco Fraschini 6 , Enrico Caneva 7 , Roberto Sitia 1, , Giovanna Musco 3 , Fabio Ciceri 4 & Simone Cenci 1,
1San Raffaele Scientific Institute, Milan, Italy; 2Università Vita-Salute San Raffaele, Milan, Italy; 3Dulbecco Telethon Institute, San Raffaele Scientific Institute, Milan, Italy; 4Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; 5Università Campus Bio-Medico di Roma, Rome, Italy; 6Department of Orthopaedics and Traumatology, San Raffaele Scientific Institute, Milan, Italy; 7Centro Interdipartimentale Grandi Apparecchiature, Università di Milano, Milan, Italy.
Multiple myeloma is an incurable neoplastic disorder of plasma cells, which invade the bone marrow, secrete monoclonal immunoglobulins, and induce bone lesions, hypercalcemia, anemia and renal failure. The development of myeloma relies on vicious interactions with the bone microenvironment, a deeper knowledge of which is needed to identify prognostic markers and potential therapeutic targets. To achieve an unbiased, comprehensive assessment of the extracellular milieu of myeloma, we performed metabolic profiling of patient-derived peripheral and bone marrow plasma by ultra high performance liquid/gas chromatography and mass spectrometry (UHPLC/GC–MS). Moreover, in order to address the local heterogeneity of myeloma bone disease, we also set up to investigate myeloma lesions by HR-MAS NMR on primary tissue specimens.
In multivariate analyses, UHPLC/GC–MS metabolic profiling of both peripheral and bone marrow plasma successfully discriminated active disease from control conditions (health, MGUS or remission), and correlated with bone marrow plasma cell counts. Independent disease vs control comparisons consistently identified a panel of metabolic alterations hallmarking active disease, including increased levels of the complement C3f peptide, HWESASLL, of specific aminoacid metabolites, including sarcosine and hydroxy-kynurenine, and decreased lysophosphocholines. Ad hoc in vitro tests on cell lines and patient-derived myeloma cells revealed a previously unsuspected trophic function of lysophosphocholines on malignant plasma cells. HR-MAS NMR metabolic fingerprinting of primary specimens efficiently matched histological findings, clustering according to tissue identity, with high concentration of lipids in tumor-rich areas, holding prognostic potential.
By providing the first metabolic fingerprinting of the bone marrow environment, our metabolomic study offers relevant information on the complex interactions established by multiple myeloma with the bone marrow environment. In particular, it identifies unanticipated disease markers for development of more accurate early diagnostic strategies, and discloses previously unpredicted pathogenic pathways as possible therapeutic targets.
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ISSN 2052-1219 (online)
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