Clonal competition with alternating dominance in multiple myeloma
Clonal competition with alternating dominance in multiple myeloma
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DOI：
10.1182/blood-2012-01-405985
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发表时间：
2012-08-02
期刊：
影响因子：
20.3
通讯作者：
Bergsagel, P. Leif
中科院分区：
文献类型：
--
作者：
Keats, Jonathan J.;Chesi, Marta;Bergsagel, P. Leif
新出现的证据表明，肿瘤可以在患者的病程中遵循几条进化路径。通过对28例多发性骨髓瘤患者病程中不同时间点采集的样本进行系列基因组分析，我们发现标准风险患者的基因组随时间推移几乎没有变化，而细胞遗传学高风险患者的基因组随时间推移显示出明显更多的变化。结果表明，存在3种时间肿瘤类型，它们可以是遗传稳定的，线性进化的，或具有移动的优势克隆的异质克隆混合物。在整个疾病过程中在7个时间点取样的一个高风险患者的详细分析鉴定了2个竞争亚克隆，其以来回交替的方式与治疗一起占优势，直到一个克隆经历了戏剧性的线性进化。通过使用骨髓瘤的Vk*MYC基因工程小鼠模型，我们模拟了亚克隆之间自发发生的优势竞争和治疗选择。（血。2012; 120（5）：1067-1076）
Emerging evidence indicates that tumors can follow several evolutionary paths over a patient's disease course. With the use of serial genomic analysis of samples collected at different points during the disease course of 28 patients with multiple myeloma, we found that the genomes of standard-risk patients show few changes over time, whereas those of cytogenetically high-risk patients show significantly more changes over time. The results indicate the existence of 3 temporal tumor types, which can either be genetically stable, linearly evolving, or heterogeneous clonal mixtures with shifting predominant clones. A detailed analysis of one high-risk patient sampled at 7 time points over the entire disease course identified 2 competing subclones that alternate in a back and forth manner for dominance with therapy until one clone underwent a dramatic linear evolution. With the use of the Vk*MYC genetically engineered mouse model of myeloma we modeled this competition between subclones for predominance occurring spontaneously and with therapeutic selection. (Blood. 2012; 120(5): 1067-1076)