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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2015; 7(1): 84-95
Published online Jan 26, 2015. doi: 10.4252/wjsc.v7.i1.84
Identify multiple myeloma stem cells: Utopia?
Ilaria Saltarella, Aurelia Lamanuzzi, Antonia Reale, Angelo Vacca, Roberto Ria
Ilaria Saltarella, Aurelia Lamanuzzi, Antonia Reale, Angelo Vacca, Roberto Ria, Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari “Aldo Moro” Medical School, Policlinico, I-70124 Bari, Italy
Author contributions: All authors made a substantial contribution to the conception and design of the manuscript, drafting the article or revising it; Saltarella I and Lamanuzzi A equally contribute to the manuscript.
Supported by Associazione Italiana per la Ricerca sul Cancro, AIRC 5 × 1000 Molecular Clinical Oncology Special Program, Milan, IT, No. 9965; by the European Commission’s Seventh Framework Programme (EU FPT7) under grant agreement No. 278706 (OVERMyR); and by MIUR PRIN 2010NECHBX
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Roberto Ria, MD, Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari “Aldo Moro” Medical School, Policlinico, Piazza Giulio Cesare, 11, I-70124 Bari, Italy. roberto.ria@uniba.it
Telephone: +39-80-5593106 Fax: +39-80-5478859
Received: July 29, 2014
Peer-review started: July 30, 2014
First decision: September 28, 2014
Revised: October 14, 2014
Accepted: October 28, 2014
Article in press: December 16, 2014
Published online: January 26, 2015
Processing time: 169 Days and 11.5 Hours
Abstract

Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells (CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activates stemness signaling (Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs.

Keywords: Bone marrow microenvironment; Cancer stem cells; Multiple myeloma; Stem cells niche; Stemness

Core tip: Multiple myeloma is a still incurable malignancy. Several study about multiple myeloma cancer stem cells showed their ability of self-renewal, survival and drug resistance. Besides, these cells are able to initiate and develop tumor when transferred into mice recipients. So understanding multiple myeloma cancer stem cells mechanisms becomes important to design new efficient targeting strategies for multiple myeloma. The aim of this review is to elucidate the state of art about multiple myeloma cancer stem cells and their critical role in maintenance of disease.