Kellner Joshua, Liu Bei, Kang Yubin, Li Zihai
Hollings Cancer Center, 29425 Charleston, SC, USA.
J Hematol Oncol. 2013 Dec 7;6:91. doi: 10.1186/1756-8722-6-91.
Multiple myeloma (MM) is a debilitating disease of proliferating and malignant plasma cells that is currently incurable. The ability of monoclonal recurrence of disease suggests it might arise from a stem cell-like population capable of self-renewal. The difficulty to isolate the cancer stem-like cell in MM has introduced confusion toward this hypothesis. However, recent evidence has suggested that MM originates from the B cell lineage with memory-B cell like features, allowing for self-renewal of the progenitor-like status and differentiation to a monoclonal plasma cell population. Furthermore, this tumor-initiating cell uses signaling pathways and microenvironment similar to the hematopoietic stem cell, though hijacking these mechanisms to create and favor a more tumorigenic environment. The bone marrow niche allows for pertinent evasion, either through avoiding immunosurveillance or through direct interaction with the stroma, inducing quiescence and thus drug resistance. Understanding the interaction of the MM stem cell to the microenvironment and the mechanisms utilized by various stem cell-like populations to allow persistence and therapy-resistance can enable for better targeting of this cell population and potential eradication of the disease.
多发性骨髓瘤（MM）是一种由增殖性恶性浆细胞引起的使人衰弱的疾病，目前无法治愈。疾病单克隆复发的能力表明它可能源于具有自我更新能力的干细胞样群体。在MM中分离癌症干细胞样细胞的困难给这一假说带来了困惑。然而，最近的证据表明，MM起源于具有记忆B细胞样特征的B细胞谱系，允许祖细胞样状态的自我更新并分化为单克隆浆细胞群体。此外，这种肿瘤起始细胞使用与造血干细胞相似的信号通路和微环境，尽管它劫持这些机制来创造并支持一个更具致瘤性的环境。骨髓生态位通过避免免疫监视或通过与基质直接相互作用，诱导静止从而产生耐药性，实现相关的逃逸。了解MM干细胞与微环境的相互作用以及各种干细胞样群体用于实现持续存在和治疗抗性的机制，能够更好地靶向该细胞群体并有可能根除这种疾病。
