Multiple myeloma (MM) is characterized by a population of functionally heterogeneous cells, in which identifying the target cells causing molecular lesion is a fundamental issue. The resultant tumor stem/progenitor cells comprise only a minor portion of the myeloma cells, which give rise through differentiation to more committed progenitors as well as differentiated blasts that constitute the bulk of the tumor. Although they are rare as compared with fully differentiated plasma cells, MM stem/progenitor cells are likely responsible for the maintenance and progression of disease through the production of new tumor cells. Thus, this is the cell population which must be eradicated for successful treatment. This article reviewed apparently conflicting evidence pertaining to the cellular origins of MM and proposed that myeloma may originate in more cellular components. In this article, the nature of the target cells, the identification and phenotypic analyses of clonogenic myeloma cells, the signaling pathways within myeloma stem/progenitor cells and the target therapy related were reviewed as well.
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