Princess Margaret Hospital, Department of Medical Oncology and Hematology, Toronto, ON, CA.
Clin Lymphoma Myeloma Leuk. 2013 Oct;13(5):552-8. doi: 10.1016/j.clml.2013.05.005. Epub 2013 Jul 12.
Multiple myeloma (MM) is a plasma cell disorder characterized by the presence of specific genetic and cytogenetic aberrations that define unique subgroups with different outcomes. On the basis of the ploidy status, MM can be subdivided into hyperdiploid MM (H-MM) and non-hyperdiploid MM (NH-MM). NH-MM is an entity that encompasses hypodiploid, pseudodiploid, and near tetraploid MM and is associated with a higher number of immunoglobulin heavy-chain (IgH) translocations.
We have systematically analyzed the structure of the karyotypic evolution in NH-MM and identified several genetic features of their complex karyotypic patterns.
On the basis of statistical models used in complex karyotypes, we were able to identify the temporal order in which the genetic aberrations occur in NH-MM. In this analysis, whole chromosome losses and IgH translocations were commonly seen, and -13/13q- and t14q32 were defined as early genetic events in the karyotypic evolution of NH-MM. Furthermore, chromosome 1 and 17 abnormalities were associated with a late karyotypic phase of evolution consistent with the recognized pattern of acquired events deemed to be associated with these type of genetic aberrations.
Accumulation of genetic aberrations in NH-MM above a threshold results in malignant transformation.
多发性骨髓瘤（MM）是一种浆细胞疾病，其特征是存在特定的遗传和细胞遗传学异常，这些异常定义了具有不同结果的独特亚群。根据ploidy 状态，MM 可分为超二倍体 MM（H-MM）和非超二倍体 MM（NH-MM）。NH-MM 是一种包含亚二倍体、假二倍体和近四倍体 MM 的实体，与更多的免疫球蛋白重链（IgH）易位相关。
我们系统地分析了 NH-MM 中核型进化的结构，并确定了其复杂核型模式的一些遗传特征。
基于复杂核型中使用的统计模型，我们能够确定 NH-MM 中遗传异常发生的时间顺序。在这项分析中，常见的是整条染色体缺失和 IgH 易位，-13/13q-和 t14q32 被定义为 NH-MM 核型进化中的早期遗传事件。此外，染色体 1 和 17 的异常与晚期核型进化阶段相关，这与公认的获得性事件模式一致，这些获得性事件被认为与这些类型的遗传异常相关。
NH-MM 中遗传异常的积累超过一定阈值会导致恶性转化。
