title: Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20.
abstract: The relationship between bone marrow (BM) cytokine and chemokine levels, cytogenetic profiles and skeletal involvement in multiple myeloma (MM) patients is not yet defined. This study investigated a cohort of 455 patients including monoclonal gammopathy of uncertain significance (MGUS), smoldering MM and symptomatic MM patients. Skeletal surveys, positron emission tomography (PET)/computerized tomography (CT) and magnetic resonance imaging (MRI) were used to identify myeloma bone disease. Significantly higher median BM levels of both C-C motif Ligand (CCL)3 and CCL20 were found in MM patients with radiographic evidence of osteolytic lesions as compared with those without, and in all MM patients with positive PET/CT scans. BM levels of CCL3, CCL20, Activin-A and Dickkopf-1 (DKK-1) were significantly higher in patients with high bone disease as compared with patients with low bone disease. Moreover, CCL20 BM levels were significant predictors of osteolysis on X-rays by multivariate logistic analysis. On the other hand, DKK-1 levels were related to the presence of MRI lesions independently of the osteolysis at the X-rays. Our data define the relationship between bone disease and the BM cytokine and chemokine patterns highlighting the tight relationship between CCL20 BM levels and osteolysis in MM.
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.|Hematology and BMT Center, Azienda Ospedaliero-Universitaria Parma, Parma, Italy.
authors.forename: B Dalla
authors.initials: BD
authors.lastname: Palma
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Guasco
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.|Clinica e Terapia Medica, Azienda Ospedaliero-Universitaria Parma, Parma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pedrazzoni
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bolzoni
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Accardi
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Costa
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sammarelli
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Craviotto
authors.affiliation: Radiology Unit, University of Parma, Parma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: De Filippo
authors.affiliation: Nuclear Medicine Unit, Azienda Ospedaliero-Universitaria Parma, Parma, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ruffini
authors.affiliation: Myeloma Unit, Division of Hematology, University of Torino, Torino, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Omedè
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Internal Medicine, University of Bari, Bari, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ria
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.|Hematology and BMT Center, Azienda Ospedaliero-Universitaria Parma, Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Aversa
authors.affiliation: Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.|Hematology and BMT Center, Azienda Ospedaliero-Universitaria Parma, Parma, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Giuliani
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000276:immunology*; D054418:Chemokine CCL20 / Q000502:physiology*; D054405:Chemokine CCL3 / Q000032:analysis; D018925:Chemokines / Q000032:analysis*; D002869:Chromosome Aberrations; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000235:genetics / Q000276:immunology*; D010014:Osteolysis / Q000209:etiology*; D053244:Osteoprotegerin / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis
chemical_list: C108355:CCL20 protein, human; C515429:CCL3 protein, human; D054418:Chemokine CCL20; D054405:Chemokine CCL3; D018925:Chemokines; D016207:Cytokines; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human