Abe Masahiro, Harada Takeshi, Matsumoto Toshio
Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Sciences, Tokushima, Japan.
Stem Cells. 2014 May;32(5):1067-73. doi: 10.1002/stem.1643.
Multiple myeloma (MM) remains incurable despite recent advances in the treatment of MM. Although the idea of MM cancer stem cells (CSCs) has been proposed for the drug resistance in MM, MM CSCs have not been properly defined yet. Besides clonotypic B cells, phenotypically distinct MM plasma cell fractions have been demonstrated to possess a clonogenic capacity, leading to long-lasting controversies regarding the cells of origin in MM or MM-initiating cells. However, MM CSCs may not be a static population and survive as phenotypically and functionally different cell types via the transition between stem-like and non-stem-like states in local microenvironments, as observed in other types of cancers. Targeting MM CSCs is clinically relevant, and different approaches have been suggested to target molecular, metabolic and epigenetic signatures, and the self-renewal signaling characteristic of MM CSC-like cells.
尽管多发性骨髓瘤(MM)的治疗最近取得了进展,但它仍然无法治愈。虽然已经提出MM癌症干细胞(CSC)的概念来解释MM中的耐药性,但MM CSC尚未得到恰当定义。除了克隆型B细胞外,表型不同的MM浆细胞亚群已被证明具有克隆能力,这导致了关于MM起源细胞或MM起始细胞的长期争议。然而,正如在其他类型癌症中所观察到的,MM CSC可能不是一个静态群体,而是通过在局部微环境中干细胞样状态和非干细胞样状态之间的转变,以表型和功能不同的细胞类型存活。靶向MM CSC具有临床相关性,并且已经提出了不同的方法来靶向分子、代谢和表观遗传特征,以及MM CSC样细胞的自我更新信号特征。