文章：

在BALB/c小鼠中，由cMYC与KRAS12V协同解除管制驱动的一种新型快速发作的高外显率浆细胞瘤小鼠模型

A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice

原文发布日期：2013-11-01

DOI: 10.1038/bcj.2013.53

类型: Original Article

开放获取: 是

英文摘要：

Our goal is to develop a rapid and scalable system for functionally evaluating deregulated genes in multiple myeloma (MM). Here, we forcibly expressed human cMYC and KRAS12V in mouse T2 B cells (IgM+B220+CD38+IgD+) using retroviral transduction and transplanted these cells into lethally irradiated recipient mice. Recipients developed plasmacytomas with short onset (70 days) and high penetrance, whereas neither cMYC nor KRAS12V alone induced disease in recipient mice. Tumor cell morphology and cell surface biomarkers (CD138+B220−IgM−GFP+) indicate a plasma cell neoplasm. Gene set enrichment analysis further confirms that the tumor cells have a plasma cell gene expression signature. Plasmacytoma cells infiltrated multiple loci in the bone marrow, spleen and liver; secreted immunoglobulins; and caused glomerular damage. Our findings therefore demonstrate that deregulated expression of cMYC with KRAS12V in T2 B cells rapidly generates a plasma cell disease in mice, suggesting utility of this model both to elucidate molecular pathogenesis and to validate novel targeted therapies.

摘要翻译： 

我们的目标是开发一个快速、可扩展的系统，用于功能性评估多发性骨髓瘤（MM）中失调基因的作用。通过逆转录病毒转导技术，我们将人类cMYC和KRAS12V基因强制表达于小鼠T2 B细胞（IgM+B220+CD38+IgD+），并将这些细胞移植至经致死剂量辐射处理的受体小鼠体内。受体小鼠在短期内（70天）高发率地形成浆细胞瘤，而单独表达cMYC或KRAS12V均未诱发疾病。肿瘤细胞形态学特征与表面生物标志物（CD138+B220−IgM−GFP+）表明其为浆细胞性肿瘤。基因集富集分析进一步证实肿瘤细胞具有浆细胞基因表达特征。浆细胞瘤细胞浸润骨髓、脾脏及肝脏多个位点，分泌免疫球蛋白，并引发肾小球损伤。本研究证实cMYC与KRAS12V在T2 B细胞中的协同失调表达可快速诱发小鼠浆细胞疾病，提示该模型在解析分子发病机制及验证新型靶向疗法方面具有应用价值。

原文链接：

A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice