文章：

人类HMGA2蛋白在小鼠中过表达可诱发前体T细胞淋巴母细胞白血病

Human HMGA2 protein overexpressed in mice induces precursor T-cell lymphoblastic leukemia

原文发布日期：2014-07-11

DOI: 10.1038/bcj.2014.46

类型: Original Article

开放获取: 是

英文摘要：

T-cell acute lymphoblastic leukemia (T-ALL) is a neoplasia of thymocytes characterized by the rapid accumulation of the precursors of T lymphocytes. HMGA2 (high-mobility group AT-hook 2) gene expression is extremely low in normal adult tissues, but it is overexpressed in many tumors. To identify the biological function of HMGA2, we generated transgenic mice carrying the human HMGA2 gene under control of the VH promoter/Eμ enhancer. Approximately 90% of Eμ-HMGA2 transgenic mice became visibly sick between 4 and 8 months due to the onset and progression of a T-ALL-like disease. Characteristic features included severe alopecia (30% of mice); enlarged lymph nodes and spleen; and profound immunological abnormalities (altered cytokine levels, hypoimmunoglobulinemia) leading to reduced immune responsiveness. Immunophenotyping showed accumulation of CD5+CD4+, CD5+CD8+ or CD5+CD8+CD4+ T-cell populations in the spleens and bone marrow of sick animals. These findings show that HMGA2-driven leukemia in mice closely resembles spontaneous human T-ALL, indicating that HMGA2 transgenic mice should serve as an important model for investigating basic mechanisms and potential new therapies of relevance to human T-ALL.

摘要翻译： 

T细胞急性淋巴细胞白血病（T-ALL）是一种胸腺细胞肿瘤，其特征是T淋巴细胞前体的快速积聚。HMGA2（高迁移率族AT-hook 2）基因在正常成人组织中表达极低，但在多种肿瘤中过度表达。为探究HMGA2的生物学功能，我们培育了在VH启动子/Eμ增强子调控下携带人源HMGA2基因的转基因小鼠。约90%的Eμ-HMGA2转基因小鼠在4至8个月内因T-ALL样疾病的发作和进展出现明显病态。典型特征包括：严重脱发（30%小鼠）；淋巴结和脾脏肿大；以及导致免疫应答减弱的深度免疫异常（细胞因子水平改变、低免疫球蛋白血症）。免疫表型分析显示患病小鼠脾脏和骨髓中积聚CD5+CD4+、CD5+CD8+或CD5+CD8+CD4+T细胞群体。这些发现表明HMGA2驱动的小鼠白血病与人类自发性T-ALL高度相似，提示HMGA2转基因小鼠可作为研究人类T-ALL相关基础机制及潜在新疗法的重要模型。

原文链接：

Human HMGA2 protein overexpressed in mice induces precursor T-cell lymphoblastic leukemia