Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109-0936, USA.
Oncogene. 2013 Jun 6;32(23):2805-17. doi: 10.1038/onc.2012.411. Epub 2012 Sep 24.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and remains incurable with conventional chemotherapy treatment approaches. CLL as a disease entity is defined by a relatively parsimonious set of diagnostic criteria and therefore likely constitutes an umbrella term for multiple related illnesses. Of the enduring fundamental biological processes that affect the biology and clinical behavior of CLL, few are as central to the pathogenesis of CLL as recurrent acquired genomic copy number aberrations (aCNA) and recurrent gene mutations. Here, a state-of-the-art overview of the pathological anatomy of the CLL genome is presented, including detailed descriptions of the anatomy of aCNA and gene mutations. Data from SNP array profiling and large-scale sequencing of large CLL cohorts, as well as stimulated karyotyping, are discussed. This review is organized by discussions of the anatomy, underlying pathomechanisms and clinical significance of individual genomic lesions and recurrent gene mutations. Finally, gaps in knowledge regarding the biological and clinical effects of recurrent genomic aberrations or gene mutations on CLL are outlined to provide critical stimuli for future research.
慢性淋巴细胞白血病（CLL）是西方世界最常见的白血病，用传统的化疗治疗方法仍然无法治愈。CLL 作为一种疾病实体，其诊断标准相对简洁，因此可能构成多个相关疾病的总称。在影响 CLL 生物学和临床行为的持久基本生物学过程中，很少有像反复获得的基因组拷贝数异常（aCNA）和反复发生的基因突变那样对 CLL 的发病机制如此重要。在这里，介绍了 CLL 基因组的病理解剖学的最新概述，包括对 aCNA 和基因突变的详细描述。讨论了 SNP 阵列分析和大型 CLL 队列的大规模测序以及刺激核型分析的数据。本综述通过讨论单个基因组病变和反复发生的基因突变的解剖结构、潜在的发病机制和临床意义进行组织。最后，概述了关于反复发生的基因组异常或基因突变对 CLL 的生物学和临床影响的知识空白，为未来的研究提供了关键的刺激。
