文章：

多发性骨髓瘤中的t（4;14）易位和FGFR3过表达：预后意义和当前临床策略

The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies

原文发布日期：2012-09-07

DOI: 10.1038/bcj.2012.37

类型: Original Article

开放获取: 是

英文摘要：

Multiple myeloma (MM) is a heterogeneous plasma cell disorder characterized by genetic abnormalities, including chromosomal translocations, deletions, duplications and genetic mutations. Translocations involving the immunoglobulin heavy chain region at chromosome 14q32 are observed in approximately 40% of patients with MM. Translocation of oncogenes into this region may lead to their increased expression, contributing to disease initiation, disease progression and therapeutic resistance. The t(4;14) translocation is associated with upregulation of the fibroblast growth factor receptor 3 (FGFR3) and the myeloma SET domain protein. Patients with t(4;14) demonstrate an overall poor prognosis that is only partially mitigated by the use of the novel agents bortezomib and lenalidomide; as such, an unmet medical need remains for patients with this aberration. Preclinical studies of inhibitors of FGFR3 have shown promise in t(4;14) MM, and these studies have led to the initiation of clinical trials. Data from these trials will help to determine the clinical utility of FGFR3 inhibitors for patients with t(4;14) MM and may pave the way for personalized medicine in patients with this incurable disease.

摘要翻译： 

多发性骨髓瘤（MM）是一种异质性浆细胞疾病，其特征为遗传学异常，包括染色体易位、缺失、重复及基因突变。约40%的MM患者可观察到涉及14号染色体q32区免疫球蛋白重链区域的易位。癌基因易位至该区域可能导致其表达增强，从而推动疾病发生、进展及治疗抵抗。t(4;14)易位与成纤维细胞生长因子受体3（FGFR3）及骨髓瘤SET结构域蛋白的上调相关。携带t(4;14)易位的患者总体预后较差，即使使用硼替佐米和来那度胺等新型药物仅能部分改善预后；因此，这类异常患者仍存在未满足的医疗需求。FGFR3抑制剂的临床前研究在t(4;14)多发性骨髓瘤中展现出潜力，这些研究已推动临床试验的启动。相关试验数据将有助于确定FGFR3抑制剂对t(4;14)多发性骨髓瘤患者的临床价值，并可能为这一难治性疾病的个体化治疗开辟道路。

原文链接：

The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies