BGI-Shenzhen, Shenzhen 518083, China.
State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China.
Nat Commun. 2016 Dec 16;7:13765. doi: 10.1038/ncomms13765.
Chronic lymphocytic leukaemia (CLL) is a frequent B-cell malignancy, characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single-nucleotide polymorphism microarray analyses of a single CLL patient over 29 years of observation and treatment, and transcriptome and whole-genome sequencing at selected time points. We identify chromosome alterations 13q14-, 6q- and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and chromosome 10 copy-neutral loss of heterogeneity that marks a major population dominant at death. Serial single-cell RNA sequencing reveals an expression pattern with high FOS, JUN and KLF4 at disease acceleration, which resolves following therapy, but reoccurs following relapse and death. Transcriptome evolution indicates complex changes in expression occur over time. In conclusion, CLL can evolve gradually during indolent phases, and undergo rapid changes following therapy.
慢性淋巴细胞白血病（CLL）是一种常见的 B 细胞恶性肿瘤，其特征是反复出现体细胞染色体改变和低水平点突变。在这里，我们展示了对一名 CLL 患者进行 29 年观察和治疗的单核苷酸多态性微阵列分析，以及在选定时间点进行的转录组和全基因组测序。我们在早期细胞克隆中发现了染色体 13q14-、6q-和 12q+的改变，治疗后克隆群体的消除，以及随后出现包含三体 12 和染色体 10 拷贝中性异质性缺失的克隆，这标志着死亡时主要的优势群体。连续的单细胞 RNA 测序显示出疾病加速时 FOS、JUN 和 KLF4 表达水平高的表达模式，治疗后会缓解，但在复发和死亡后会再次出现。转录组进化表明随着时间的推移表达会发生复杂的变化。总之，CLL 在惰性阶段可以逐渐进化，并且在治疗后会发生快速变化。
