title: Identify multiple myeloma stem cells: Utopia?
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.
authors.affiliation: 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.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Saltarella
authors.affiliation: 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.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Lamanuzzi
authors.affiliation: 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.
authors.forename: Antonia
authors.initials: A
authors.lastname: Reale
authors.affiliation: 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.
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ria
keywords: Bone marrow microenvironment; Cancer stem cells; Multiple myeloma; Stem cells niche; Stemness