Leukemia-related transcription factor TEL/ETV6 expands erythroid precursors and stimulates hemoglobin synthesis
Leukemia-related transcription factor TEL/ETV6 expands erythroid precursors and stimulates hemoglobin synthesis
复制标题
DOI：
10.1111/j.1349-7006.2009.01097.x
复制
发表时间：
2009-04-01
期刊：
影响因子：
5.7
通讯作者：
Mitani, Kinuko
中科院分区：
文献类型：
--
作者：
Eguchi-Ishimae, Minenori;Eguchi, Mariko;Mitani, Kinuko
TEL/ETV6位于染色体12p13上，编码E26转化特异性转录因子家族的一个成员。已知TEL在多种白血病和实体瘤中被重排，导致致癌嵌合蛋白的形成。Tel对于维持骨髓中的造血干细胞至关重要。为了了解TEL在红细胞生成中的作用，我们培育了在红系分化过程中激活的Gata1启动子控制下表达人TEL的转基因小鼠（Gata1 -TEL转基因小鼠）。尽管GATA1-TEL转基因小鼠在18月龄前表现健康，但与非转基因小鼠相比，转基因小鼠的血红蛋白水平更高。此外，CD71(+)/TER119（+）和c-kit(+)/CD41（+）群体分别在促红细胞生成素和血小板生成素存在下培养骨髓细胞时，在转基因小鼠中增殖频率更高。在转基因小鼠中，血红细胞中α -e和β -主珠蛋白基因的表达增强。当在相同Gata1启动子下表达人TEL的胚胎干细胞分化为造血细胞时，从红细胞爆裂形成单位的数量来看，未成熟红细胞前体比对照组增加得更好。我们的发现提示TEL在红细胞前体扩张和血红蛋白积累中起一定作用。（癌症科学2009；100:689-697）
TEL/ETV6 located at chromosome 12p13 encodes a member of the E26 transformation-specific family of transcription factors. TEL is known to be rearranged in a variety of leukemias and solid tumors resulting in the formation of oncogenic chimeric protein. Tel is essential for maintaining hematopoietic stem cells in the bone marrow. To understand the role of TEL in erythropoiesis, we generated transgenic mice expressing human TEL under the control of Gata1 promoter that is activated during the course of the erythroid-lineage differentiation (GATA1-TEL transgenic mice). Although GATA1-TEL transgenic mice appeared healthy up to 18 months of age, the level of hemoglobin was higher in transgenic mice compared to non-transgenic littermates. In addition, CD71(+)/TER119(+) and c-kit(+)/CD41(+) populations proliferated with a higher frequency in transgenic mice when bone marrow cells were cultured in the presence of erythropoietin and thrombopoietin, respectively. In transgenic mice, enhanced expression of Alas-e and beta-major globin genes was observed in erythroid-committed cells. When embryonic stem cells expressing human TEL under the same Gata1 promoter were differentiated into hematopoietic cells, immature erythroid precursor increased better compared to controls as judged from the numbers of burst-forming unit of erythrocytes. Our findings suggest some roles of TEL in expanding erythroid precursors and accumulating hemoglobin. (Cancer Sci 2009; 100: 689-697)