Leukemia-related transcription factor TEL/ETV6 expands erythroid precursors and stimulates hemoglobin synthesis

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)