TEL-AML1 promotes development of specific hematopoietic lineages consistent with preleukemic activity
TEL-AML1 promotes development of specific hematopoietic lineages consistent with preleukemic activity
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DOI：
10.1182/blood-2003-10-3695
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发表时间：
2004-05-15
期刊：
影响因子：
20.3
通讯作者：
Williams, O
中科院分区：
文献类型：
--
作者：
Morrow, M;Horton, S;Williams, O
t（12; 21）（p13; q22）易位是在任何儿科白血病中发现的最常见的染色体异常，并产生TEL-AML 1融合产物。为了研究TEL-AML 1对造血的影响，用表达该融合蛋白的逆转录病毒载体转导胎肝造血祖细胞（HPC）。我们发现，TEL-AML 1显着改变体外HPC的分化，优先促进B淋巴细胞发育，增强B细胞前体的自我更新，并导致建立长期生长因子依赖性前B细胞系。然而，它对体外骨髓发育没有影响。进行进一步的实验以确定TEL-AML 1是否也在体内显示谱系特异性活性。表达TEL-AML 1的HPC在体内重建B细胞和髓系方面表现出竞争优势，但对T细胞系的重建没有影响。尽管促进了这些造血变化，但TEL-AML 1并没有在移植小鼠中诱导白血病。我们的研究提供了一个独特的见解TEL-AML 1在白血病易感性的作用和一个潜在的模型，以研究与这种融合相关的白血病发生的机制。(C)2004年，美国血液学会。
The t(12;21)(p13;q22) translocation is the most common chromosomal abnormality yet identified in any pediatric leukemia and gives rise to the TEL-AML1 fusion product. To investigate the effects of TEL-AML1 on hematopoiesis, fetal liver hematopoietic progenitor cells (HPCs) were transduced with retroviral vectors expressing this fusion protein. We show that TEL-AML1 dramatically alters differentiation of HPCs in vitro, preferentially promoting B-lymphocyte development, enhancing self-renewal of B-cell precursors, and leading to the establishment of long-term growth factor-dependent pre-B-cell lines. However, it had no effect on myeloid development in vitro. Further experiments were performed to determine whether TEL-AML1 also demonstrates lineage-specific activity in vivo. TEL-AML1-expressing HPCs displayed a competitive advantage in reconstituting both B-cell and myeloid lineages in vivo but had no effect on reconstitution of the T-cell lineage. Despite promoting these alterations in hematopolesis, TEL-AML1 did not induce leukemia in transplanted mice. Our study provides a unique insight into the role of TEL-AML1 in leukemia predisposition and a potential model to study the mechanism of leukemo-genesis associated with this fusion. (C) 2004 by The American Society of Hematology.