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Leukemia. 2016 Feb;30(2):409-16. doi: 10.1038/leu.2015.259. Epub 2015 Sep 30.

Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20.

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Department of Clinical and Experimental Medicine, Myeloma Unit, University of Parma, Parma, Italy.
Hematology and BMT Center, Azienda Ospedaliero-Universitaria Parma, Parma, Italy.
Clinica e Terapia Medica, Azienda Ospedaliero-Universitaria Parma, Parma, Italy.
Radiology Unit, University of Parma, Parma, Italy.
Nuclear Medicine Unit, Azienda Ospedaliero-Universitaria Parma, Parma, Italy.
Myeloma Unit, Division of Hematology, University of Torino, Torino, Italy.
Department of Biomedical Sciences and Human Oncology, Internal Medicine, University of Bari, Bari, Italy.


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.

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