Identify multiple myeloma stem cells： Utopia？

Multiple myeloma （MM） is a hematologic malignancy ofmonoclonal plasma cells which remains incurable despiterecent advances in therapies. The presence of cancerstem cells （CSCs） has been demonstrated in many solidand hematologic tumors, so the idea of CSCs has beenproposed for MM, even if MM CSCs have not been defineyet. The existence of myeloma CSCs with clonotypicB and clonotypic non B cells was postulated by manygroups. This review aims to focus on these distinctclonotypic subpopulations and on their ability to developand sustain MM. The bone marrow microenvironmentprovides to MM CSCs self-renewal, survival and drugresistance thanks to the presence of normal and cancerstem cell niches. The niches and CSCs interact each otherthrough adhesion molecules and the interplay betweenligands and receptors activate stemness signaling（Hedgehog, Wnt and Notch pathways）. MM CSCs arealso supposed to be responsible for drug resistancethat happens in three steps from the initial cancer cellhoming microenvironment-mediated to development ofmicroenvironment-independent drug resistance. In thisreview, we will underline all these aspects of MM CSCs.