title: Cutaneous localization in multiple myeloma in the context of bortezomib-based treatment: how do myeloma cells escape from the bone marrow to the skin?
abstract: The skin is a possible site of extramedullary localization in multiple myeloma (MM) patients; however, the mechanisms involved in this process are poorly understood. We describe the case of a refractory MM patient who developed a cutaneous localization under bortezomib treatment and we further expanded observations in other eight MM patients. We focused on the expression of genes involved in plasma cell skin homing, including CCR10, which was highly expressed. Moreover, we observed a lack of CXCR4 surface expression and the down-regulation of ICAM1/CD54 throughout the progression of the disease, suggesting a possible mechanism driving the escape of MM cells from the bone marrow into the skin.
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marchica
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126, Parma, Italy.|"Ematologia e CTMO", "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Accardi
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Storti
authors.affiliation: Pathology Unit, "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mancini
authors.affiliation: Pathology Unit, "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Martella
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126, Parma, Italy.|"Ematologia e CTMO", "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Dalla Palma
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126, Parma, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Bolzoni
authors.affiliation: Laboratory of Pre-clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Todoerti
authors.affiliation: Haematopathology Diagnostic Area- Pathology Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Magda
authors.initials: M
authors.lastname: Marcatti
authors.affiliation: "Ematologia e CTMO", "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Schifano
authors.affiliation: "Ematologia e CTMO", "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bonomini
authors.affiliation: "Ematologia e CTMO", "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sammarelli
authors.affiliation: Department of Oncology and Hemato-Oncology, University of Milano, Milan, Italy.|Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
authors.affiliation: Haematopathology Diagnostic Area- Pathology Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126, Parma, Italy.|"Ematologia e CTMO", "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126, Parma, Italy. nicola.giuliani@unipr.it.|"Ematologia e CTMO", "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy. nicola.giuliani@unipr.it.
authors.forename: Nicola
authors.identifier: http://orcid.org/0000-0003-3457-3774
authors.initials: N
authors.lastname: Giuliani
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D000069286:Bortezomib / Q000627:therapeutic use*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D010950:Plasma Cells / Q000187:drug effects / Q000473:pathology*; D010954:Plasmacytoma / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D019718:Receptors, CXCR4 / Q000235:genetics; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary*
chemical_list: D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; C573420:ICAM1 protein, human; D019718:Receptors, CXCR4; D018799:Intercellular Adhesion Molecule-1; D000069286:Bortezomib
keywords: Bone marrow; Extramedullary disease; Multiple myeloma; Skin homing