Yaccoby Shmuel
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR.
Clin Lymphoma Myeloma Leuk. 2018 Jan;18(1):38-43. doi: 10.1016/j.clml.2017.09.020. Epub 2017 Oct 3.
The identity of so-called malignant stem cells in multiple myeloma has long been controversial. However, it is now appreciated that a small population of myeloma cells has a stem-like capacity for self-renewal and resides within the population of recognizable myeloma plasma cells, although whether these cells are quiescent or proliferative remains unresolved. It is also now accepted that subpopulations of myeloma plasma cells alternate bidirectionally and dynamically between immature and mature phenotypes, and both subpopulations are capable of clonogenicity in vitro and in animal models. Mounting evidence suggests that in multiple myeloma, small populations of quiescent myeloma stem cells behave as tumor-initiating cells as a result of their interaction with the endosteal bone marrow niche. However, a different, small population of proliferative myeloma stem cells produces the tumor bulk, and this population is likely responsible for the emergence of evolved subclones. A cellular-based plasticity model in which 2 states of stem-like cell compartments-quiescent and proliferative-exist simultaneously and are regulated dynamically by the microenvironment, epigenetics, and genetic aberrations may explain various clinical scenarios and the lack of consensus among some reported studies.
多发性骨髓瘤中所谓恶性干细胞的身份长期以来一直存在争议。然而，现在人们认识到，一小部分骨髓瘤细胞具有类似干细胞的自我更新能力，存在于可识别的骨髓瘤浆细胞群体中，尽管这些细胞是静止的还是增殖的仍未解决。现在也已公认，骨髓瘤浆细胞亚群在未成熟和成熟表型之间双向动态交替，并且这两个亚群在体外和动物模型中都具有克隆形成能力。越来越多的证据表明，在多发性骨髓瘤中，一小部分静止的骨髓瘤干细胞由于与骨内膜骨髓微环境相互作用而表现为肿瘤起始细胞。然而，另一小部分增殖性骨髓瘤干细胞产生肿瘤主体，并且这一群体可能是进化亚克隆出现的原因。一种基于细胞的可塑性模型，其中静止和增殖这两种干细胞样细胞区室状态同时存在，并由微环境、表观遗传学和基因畸变动态调节，这可能解释了各种临床情况以及一些报道研究之间缺乏共识的现象。
