International Myeloma Working Group molecular classification of multiple myeloma: spotlight review.
International Myeloma Working Group molecular classification of multiple myeloma: spotlight review.
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骨髓瘤是单克隆浆细胞的恶性增殖。虽然形态相似，但已在遗传和分子水平上鉴定出该疾病的几种亚型。这些基因亚型与独特的临床病理特征和不同的结果相关。在最高层次水平，骨髓瘤可分为超二倍体和非超二倍体亚型。后者主要由携带IgH易位的病例组成，通常与更具侵袭性的临床特征和较短的生存期相关。骨髓瘤中的三种主要IgH易位是t（11;14）（q13;q32）、t（4;14）（p16;q32）和t（14;16）（q32;q23）。超二倍体骨髓瘤的特征是三体和更惰性的疾病形式。已经确定了许多遗传进展因素，包括13号和17号染色体的缺失和1号染色体的异常（1 p缺失和1 q扩增）。细胞存活和增殖的其他关键驱动因素也已被确定，如核因子B激活突变和细胞周期蛋白依赖性途径调节剂的其他去调节因子。对该疾病的生物学亚型的进一步理解来自于新技术的应用，如基因表达谱和基于阵列的比较基因组杂交。从这些研究中产生的数据和先前通过其他机制阐明的数据相结合，使大多数骨髓瘤病例被归类为几种遗传亚型之一。本文提出了骨髓瘤亚型分类的框架，并为基因检测提供了建议。该小组建议将基因检测纳入日常临床实践，并将其作为所有正在进行和未来临床试验的重要组成部分。
Myeloma is a malignant proliferation of monoclonal plasma cells. Although morphologically similar, several subtypes of the disease have been identified at the genetic and molecular level. These genetic subtypes are associated with unique clinico-pathological features and dissimilar outcome. At the top hierarchical level, myeloma can be divided into hyperdiploid and non-hyperdiploid subtypes. The latter is mainly composed of cases harboring IgH translocations, generally associated with more aggressive clinical features and shorter survival. The three main IgH translocations in myeloma are the t(11;14)(q13;q32), t(4;14)(p16;q32) and t(14;16)(q32;q23). Trisomies and a more indolent form of the disease characterize hyperdiploid myeloma. A number of genetic progression factors have been identified including deletions of chromosomes 13 and 17 and abnormalities of chromosome 1 (1p deletion and 1q amplification). Other key drivers of cell survival and proliferation have also been identified such as nuclear factor- B-activating mutations and other deregulation factors for the cyclin-dependent pathways regulators. Further understanding of the biological subtypes of the disease has come from the application of novel techniques such as gene expression profiling and array-based comparative genomic hybridization. The combination of data arising from these studies and that previously elucidated through other mechanisms allows for most myeloma cases to be classified under one of several genetic subtypes. This paper proposes a framework for the classification of myeloma subtypes and provides recommendations for genetic testing. This group proposes that genetic testing needs to be incorporated into daily clinical practice and also as an essential component of all ongoing and future clinical trials.