Assessing Heterogeneity of Osteolytic Lesions in Multiple Myeloma by ¹H HR-MAS NMR Metabolomics.
Multiple myeloma (MM) is a malignancy of plasma cells characterized by multifocal osteolytic bone lesions. Macroscopic and genetic heterogeneity has been documented within MM lesions. Understanding the bases of such heterogeneity may unveil relevant features of MM pathobiology. To this aim, we deployed unbiased ¹H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) metabolomics to analyze multiple biopsy specimens of osteolytic lesions from one case of pathological fracture caused by MM. Multivariate analyses on normalized metabolite peak integrals allowed clusterization of samples in accordance with a posteriori histological findings. We investigated the relationship between morphological and NMR features by merging morphological data and metabolite profiling into a single correlation matrix. Data-merging addressed tissue heterogeneity, and greatly facilitated the mapping of lesions and nearby healthy tissues. Our proof-of-principle study reveals integrated metabolomics and histomorphology as a promising approach for the targeted study of osteolytic lesions.
Biomolecular NMR Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy. tavelfuchs.laurette@hsr.it.
Laurette
L
Tavel
Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy. francesca.fontana@wustl.edu.|Università Vita-Salute San Raffaele, 20132 Milano, Italy. francesca.fontana@wustl.edu.
Francesca
F
Fontana
Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy. garciamanteiga.josemanuel@hsr.it.
Josè Manuel
JM
Garcia Manteiga
Biomolecular NMR Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy. silvia@mestrelab.com.
Silvia
S
Mari
Age Related Diseases Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy. mariani.elisabetta@hsr.it.
Elisabetta
E
Mariani
Centro Interdipartimentale Grandi Apparecchiature, Università di Milano, 20132 Milano, Italy. enrico.caneva@unimi.it.
Enrico
E
Caneva
Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy. sitia.roberto@hsr.it.|Università Vita-Salute San Raffaele, 20132 Milano, Italy. sitia.roberto@hsr.it.
Roberto
R
Sitia
Department of Orthopaedics and Traumatology, Orthopaedics, San Raffaele Scientific Institute, 20132 Milano, Italy. camnasio.francesco@hsr.it.
Francesco
F
Camnasio
Department of Oncohematology, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milano, Italy. marcatti.magda@hsr.it.
Magda
M
Marcatti
Università Vita-Salute San Raffaele, 20132 Milano, Italy. cenci.simone@hsr.it.|Age Related Diseases Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy. cenci.simone@hsr.it.
Simone
S
Cenci
Biomolecular NMR Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy. musco.giovanna@hsr.it.
Giovanna
G
Musco
D000368:Aged; D001706:Biopsy; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics / Q000379:methods*; D009101:Multiple Myeloma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015999:Multivariate Analysis; D010014:Osteolysis / Q000150:complications / Q000378:metabolism* / Q000473:pathology
high-resolution magic-angle spinning (HR-MAS); metabolomics; multiple myeloma; nuclear magnetic resonance (NMR); osteolysis