Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin
Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin
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胎儿造血调节因子 FEV 的表达表明产前白血病
DOI：
10.1038/leu.2016.313
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发表时间：
2017-05-01
期刊：
影响因子：
11.4
通讯作者：
Hong, D-L
中科院分区：
文献类型：
--
作者：
Liu, T-H;Tang, Y-J;Hong, D-L
癌症的起源与病因学以及治疗学有关。一些研究表明，儿童恶性肿瘤可能起源于子宫内。然而，目前还没有一种诊断方法来区分出生前或出生后发生的癌症。在这里，我们确定了一个转录因子FEV（第五尤因变体），在胎儿造血细胞中表达，出生后变得沉默。我们的特点是，FEV是造血干细胞（HSC）的自我更新所必需的。我们接着发现FEV在大多数婴儿白血病样本中表达，但在成人样本中很少表达，这与前者已知的产前起源雅阁。我们进一步确定了大多数儿童急性淋巴细胞白血病（ALL）和急性髓细胞白血病（AML）FEV阳性。此外，FEV敲低显著损害白血病干细胞的白血病增殖能力。因此，我们确定FEV是胎儿造血干细胞所特有的，并在产前来源的白血病细胞中稳定表达。它还可以提供易处理的治疗靶点。
The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre-or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.