多发性骨髓瘤的生物学和细胞遗传学。

P Joy Ho, Lynda J Campbell, John Gibson, Ross Brown, Douglas Joshua
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引用次数: 26

摘要

尽管我们对骨髓瘤细胞生物学的了解有所进展,但我们对骨髓瘤发病机制的了解仍然不完整。在这篇综述中,我们总结了b细胞发育和免疫球蛋白(lg)基因重排的细胞和分子方面,这对定义骨髓瘤浆细胞(MPC)的特征很重要。PMC经历了可变基因重组、体细胞超突变和同型转换,因此处于生发后的中心发育阶段。前切克隆细胞和同型变异的发现提出了关于骨髓瘤细胞起源的有趣问题,目前尚无结论性数据。然而,关于骨髓瘤的染色体和遗传畸变,包括13号单体、Ig重链(IgH)开关区易位、数值异常和多种异质变化,已经获得了很多信息。为了克服传统核型的不敏感性,已经开发了各种技术,利用分子细胞遗传学策略,从荧光原位杂交精确定位位点,通过多色光谱核型对基因组进行更“全面”的评估,到通过比较基因组杂交对特定来源的染色体物质进行定量。检测到的异常是否代表致癌损害,是否与疾病进展有关,或者仅仅是遗传不稳定的“副产品”,目前尚不清楚。对于IgH易位,候选基因如Cyclin D1和FGFR3的作用已经在动物模型中通过定量表达和评估其致癌性(例如FGFR3)进行了广泛的研究。其他畸变如c-myc、ras和p53的意义也被研究过。随着寡核苷酸微阵列的出现,可以有效地检测数千种基因的表达。到目前为止,这种方法似乎有希望定义不同疾病行为的亚群,并可能突出在骨髓瘤发病机制中重要的特定基因和分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The biology and cytogenetics of multiple myeloma.

Despite the advances in our knowledge of myeloma cell biology, our understanding of myeloma pathogenesis is still incomplete. In this review, we present a summary of the cellular and molecular aspects of B-cell development and immunoglobulin (lg) gene rearrangement which have been important in defining the characteristics of the myeloma plasma cell (MPC). The PMC has undergone variable gene recombination, somatic hypermutation and isotype switching, and is therefore at a postgerminal center stage of development. The finding of preswitch clonal cells and isotype variants have raised interesting questions about the cell of origin of myeloma, for which no conclusive data is as yet available. However much information has been obtained about the chromosomal and genetic aberrations in myeloma, including monosomy 13, Ig heavy chain (IgH) switch region translocations, numerical abnormalities and a multitude of heterogeneous changes. A variety of techniques have been developed to overcome the insensitivity of conventional karyotyping, utilizing molecular cytogenetic strategies ranging from the delineation of precise loci by fluorescent in situ hybridization, a more "global" assessment of the genome by multicolor spectral karyotyping, to the quantitation of chromosomal material of specific origin by comparative genomic hybridization. Whether the abnormalities detected represent oncogenic insults, are involved in disease progression or are simply "by-products" of genetic instability is still unclear. For IgH translocations, the role of candidate genes such as Cyclin D1 and FGFR3 has been studied extensively by quantitating their expression and assessment of their oncogenicity (e.g. for FGFR3) in animal models. The significance of other aberrations such as c-myc, ras and p53 has also been investigated. With the advent of oligonucleotide microarrays, the expression of thousands of genes can be efficiently examined. So far, this approach seems promising in defining subgroups of different disease behavior, and may highlight specific genes and molecular mechanisms which are important in myeloma pathogenesis.

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