Retroviral transduction of TLS-ERG initiates a leukemogenic program in normal human hematopoietic cells
Retroviral transduction of TLS-ERG initiates a leukemogenic program in normal human hematopoietic cells
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DOI：
10.1073/pnas.95.14.8239
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发表时间：
1998-07-07
影响因子：
11.1
通讯作者：
Dick, JE
中科院分区：
文献类型：
--
作者：
Pereira, DS;Dorrell, C;Dick, JE
由于染色体易位与特定的人类白血病之间的关联，许多嵌合癌基因已经被鉴定出来。然而，由于缺乏适当的实验系统来研究它们的功能，这些癌基因在白血病发生过程的起始期间破坏正常人类造血细胞的发育程序的生物学机制知之甚少。在这里，我们报告说，逆转录病毒转导TLS-ERG，髓性白血病相关的融合基因，人脐带血细胞的结果改变骨髓和逮捕红细胞分化和显着增加的增殖和自我更新能力的转导髓系祖细胞。因此，TLS-ERG表达单独诱导白血病的程序，表现出类似的人类疾病与此易位。这些结果提供了一个单一的癌基因诱导的人类白血病过程的早期阶段的实验检查，并建立了一个范例，功能测定推定的白血病基因在正常的人类造血细胞。
Many chimeric oncogenes have been identified by virtue of the association between chromosomal translocation and specific human leukemias. However, the biological mechanism by which these oncogenes disrupt the developmental program of normal human hematopoietic cells during the initiation of the leukemogenic process is poorly understood due to the absence of an appropriate experimental system to study their function. Here, we report that retroviral transduction of TLS-ERG, a myeloid leukemia-associated fusion gene, to human cord blood cells results in altered myeloid and arrested erythroid differentiation and a dramatic increase in the proliferative and self-renewal capacity of transduced myeloid progenitors. Thus, TLS-ERG expression alone induced a leukemogenic program that exhibited similarities to the human disease associated with this translocation. These results provide an experimental examination of the early stages of the human leukemogenic process induced by a single oncogene and establish a paradigm to functionally assay putative leukemogenic genes in normal human hematopoietic cells.