Human HMGA2 protein overexpressed in mice induces precursor T-cell lymphoblastic leukemia.
Human HMGA2 protein overexpressed in mice induces precursor T-cell lymphoblastic leukemia.
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DOI：
10.1038/bcj.2014.46
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发表时间：
2014-07-11
影响因子：
12.8
通讯作者：
Croce, C. M.
中科院分区：
文献类型：
--
作者：
Efanov, A.;Zanesi, N.;Coppola, V.;Nuovo, G.;Bolon, B.;Wernicle-Jameson, D.;Lagana, A.;Hansjuerg, A.;Pichiorri, F.;Croce, C. M.
T细胞急性淋巴细胞白血病（T-ALL）是一种以T淋巴细胞前体快速积聚为特征的胸腺细胞瘤。HMGA 2（高迁移率族AT-钩2）基因在正常成人组织中表达极低，但在许多肿瘤中过表达。为了鉴定HMGA 2的生物学功能，我们产生了在VH启动子/Eμ增强子控制下携带人HMGA 2基因的转基因小鼠。大约90%的Eμ-HMGA 2转基因小鼠由于T-ALL样疾病的发作和进展而在4至8个月之间出现明显的疾病。特征性特征包括重度脱发（30%的小鼠）;淋巴结和脾脏肿大;以及导致免疫反应性降低的严重免疫学异常（细胞因子水平改变，免疫球蛋白血症降低）。免疫表型分析显示，在患病动物的脾脏和骨髓中，CD 5 + CD 4+、CD 5 + CD 8+或CD 5 + CD 8 + CD 4 + T细胞群蓄积。这些发现表明，小鼠中HMGA 2驱动的白血病与自发性人类T-ALL非常相似，表明HMGA 2转基因小鼠应作为研究人类T-ALL相关的基本机制和潜在新疗法的重要模型。
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.
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影响因子：
50.3
作者：
Fedele, Monica;Visone, Rosa;Fusco, Alfredo
通讯作者：
Fusco, Alfredo
影响因子：
20.3
作者：
Morse, HC;Anver, MR;Ward, JM
通讯作者：
Ward, JM
影响因子：
5.2
作者：
CHANDRA, RK
通讯作者：
CHANDRA, RK
影响因子：
20.3
作者：
Lin, YW;Nichols, RA;Aplan, PD
通讯作者：
Aplan, PD
DOI：
10.1073/pnas.141224998
发表时间：
2001-07-03
影响因子：
11.1
作者：
Baldassarre, G;Fedele, M;Fusco, A
通讯作者：
Fusco, A