Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Cell Cycle. 2010 Sep 15;9(18):3792-7. doi: 10.4161/cc.9.18.13047.
Cancer is the consequence of sequential acquisition of mutations within somatic cells. Mutations alter the relative reproductive fitness of cells, enabling the population to evolve in time as a consequence of selection. Cancer therapy itself can select for or against specific subclones. Given the large population of tumor cells, subclones inevitably emerge and their fate will depend on the evolutionary dynamics that define the interactions between such clones. Using a combination of in vitro studies and mathematical modeling, we describe the dynamic behavior of two cell lines isolated from the same patient at different time points of disease progression and show how the two clones relate to one another. We provide evidence that the two clones coexisted at the time of initial presentation. The dominant clone presented with biopsy proven cardiac AL amyloidosis. Initial therapy selected for the second clone that expanded leading to a change in the diagnosis to multiple myeloma. The evolutionary dynamics relating the two cell lines are discussed and a hypothesis is generated in regard to the mechanism of one of the phenotypic characteristics that is shared by these two cell lines.
癌症是体细胞中连续获得突变的结果。突变改变了细胞的相对生殖适应性，使细胞群体能够随着选择而随时间进化。癌症治疗本身可以选择或反对特定的亚克隆。考虑到肿瘤细胞的庞大数量，亚克隆不可避免地会出现，它们的命运将取决于定义这些克隆之间相互作用的进化动态。我们使用体外研究和数学建模的组合，描述了从同一患者在疾病进展的不同时间点分离出来的两个细胞系的动态行为，并展示了这两个克隆彼此之间的关系。我们提供的证据表明，两个克隆在初始表现时就共存了。优势克隆表现为经活检证实的心脏 AL 淀粉样变性。初始治疗选择了第二个克隆，使其扩张，导致诊断变为多发性骨髓瘤。讨论了与这两个细胞系相关的进化动态，并提出了一个假设，即与这两个细胞系共享的一种表型特征的机制。
