Top

Published in:

01-01-2017 | Case Report

Cutaneous localization in multiple myeloma in the context of bortezomib-based treatment: how do myeloma cells escape from the bone marrow to the skin?

Authors: Valentina Marchica, Fabrizio Accardi, Paola Storti, Cristina Mancini, Eugenia Martella, Benedetta Dalla Palma, Marina Bolzoni, Katia Todoerti, Magda Marcatti, Chiara Schifano, Sabrina Bonomini, Gabriella Sammarelli, Antonino Neri, Maurilio Ponzoni, Franco Aversa, Nicola Giuliani

Published in: International Journal of Hematology | Issue 1/2017

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.

Available only for authorised users

Alsayed Y, Ngo H, Runnels J, Leleu X, Singha UK, Pitsillides CM, et al. Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma. Blood. 2007;109:2708–17.PubMedPubMedCentral

Vande Broek I, Vanderkerken K, Van Camp B, Van Riet I. Extravasation and homing mechanisms in multiple myeloma. Clin Exp Metastasis. 2008;25:325–34.CrossRefPubMed

Anderson KC. Multiple myeloma. Hematol Oncol Clin North Am. 2014;28:xi–xii.CrossRefPubMed

Abe M. Targeting the interplay between myeloma cells and the bone marrow microenvironment in myeloma. Int J Hematol. 2011;94:334–43.CrossRefPubMed

Blade J, Fernandez de Larrea C, Rosinol L, Cibeira MT, Jimenez R, Powles R. Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach. J Clin Oncol. 2011;29:3805–12.CrossRefPubMed

Usmani SZ, Heuck C, Mitchell A, Szymonifka J, Nair B, Hoering A, et al. Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica. 2012;97:1761–7.CrossRefPubMedPubMedCentral

Wirk B, Wingard JR, Moreb JS. Extramedullary disease in plasma cell myeloma: the iceberg phenomenon. Bone Marrow Transpl. 2013;48:10–8.CrossRef

Kunkel EJ, Butcher EC. Plasma-cell homing. Nat Rev Immunol. 2003;3:822–9.CrossRefPubMed

Requena L, Kutzner H, Palmedo G, Calonje E, Requena C, Perez G, et al. Cutaneous involvement in multiple myeloma: a clinicopathologic, immunohistochemical, and cytogenetic study of 8 cases. Arch Dermatol. 2003;139:475–86.CrossRefPubMed

10.

Floyd SR, Pantanowitz L, McDermott DF, Yannucci J, Driver JA, Stevenson MA, et al. Plasma cell problems: case 1. disseminated cutaneous plasmacytomas treated with total skin electron radiotherapy. J Clin Oncol. 2005;23:3138–40.CrossRefPubMed

11.

Nakayama T, Hieshima K, Izawa D, Tatsumi Y, Kanamaru A, Yoshie O. Cutting edge: profile of chemokine receptor expression on human plasma cells accounts for their efficient recruitment to target tissues. J Immunol. 2003;170:1136–40.CrossRefPubMed

12.

Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467–73.CrossRefPubMed

13.

Calura E, Bisognin A, Manzoni M, Todoerti K, Taiana E, Sales G, et al. Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients. Oncotarget. 2016;7:2367–78.PubMed

14.

Sachdev R, George TI, Schwartz EJ, Sundram UN. Discordant immunophenotypic profiles of adhesion molecules and cytokines in acute myeloid leukemia involving bone marrow and skin. Am J Clin Pathol. 2012;138:290–9.CrossRefPubMed

15.

Homey B, Alenius H, Muller A, Soto H, Bowman EP, Yuan W, et al. CCL27–CCR10 interactions regulate T cell-mediated skin inflammation. Nat Med. 2002;8:157–65.CrossRefPubMed

16.

Fujita Y, Abe R, Sasaki M, Honda A, Furuichi M, Asano Y, et al. Presence of circulating CCR10 + T cells and elevated serum CTACK/CCL27 in the early stage of mycosis fungoides. Clin Cancer Res. 2006;12:2670–5.CrossRefPubMed

17.

Varga C, Xie W, Laubach J, Ghobrial IM, O’Donnell EK, Weinstock M, et al. Development of extramedullary myeloma in the era of novel agents: no evidence of increased risk with lenalidomide-bortezomib combinations. Br J Haematol. 2015;169:843–50.CrossRefPubMed

18.

Blade J, Fernandez de Larrea C, Rosinol L. Extramedullary disease in multiple myeloma in the era of novel agents. Br J Haematol. 2015;169:763–5.CrossRefPubMed

19.

Dahl IM, Rasmussen T, Kauric G, Husebekk A. Differential expression of CD56 and CD44 in the evolution of extramedullary myeloma. Br J Haematol. 2002;116:273–7.CrossRefPubMed

20.

Stessman HA, Mansoor A, Zhan F, Janz S, Linden MA, Baughn LB, et al. Reduced CXCR4 expression is associated with extramedullary disease in a mouse model of myeloma and predicts poor survival in multiple myeloma patients treated with bortezomib. Leukemia. 2013;27:2075–7.CrossRefPubMedPubMedCentral

21.

Noborio-Hatano K, Kikuchi J, Takatoku M, Shimizu R, Wada T, Ueda M, et al. Bortezomib overcomes cell-adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma. Oncogene. 2009;28:231–42.CrossRefPubMed

22.

Chang TP, Poltoratsky V, Vancurova I. Bortezomib inhibits expression of TGF-beta1, IL-10, and CXCR4, resulting in decreased survival and migration of cutaneous T cell lymphoma cells. J Immunol. 2015;194:2942–53.CrossRefPubMedPubMedCentral

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?
Authors: Valentina Marchica
Fabrizio Accardi
Paola Storti
Cristina Mancini
Eugenia Martella
Benedetta Dalla Palma
Marina Bolzoni
Katia Todoerti
Magda Marcatti
Chiara Schifano
Sabrina Bonomini
Gabriella Sammarelli
Antonino Neri
Maurilio Ponzoni
Franco Aversa
Nicola Giuliani
Publication date: 01-01-2017
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 1/2017
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-016-2104-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

ACC 2024 Congress

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2017

Disease characteristics and prognosis of myelodysplastic syndrome presenting with isolated thrombocytopenia

Multifaceted role of the polycomb-group gene EZH2 in hematological malignancies

Analysis of thrombosis and bleeding complications in patients with polycythemia vera: a Turkish retrospective study

A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in patients with refractory febrile neutropenia

Leaving IJH: joining to fly

Chronic NK lymphocytosis identified by a distinct immunophenotypic pattern

Keynote webinar | Spotlight on antibody–drug conjugates in cancer