Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin.
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ICR Authors
Authors
Liu, T-H
Tang, Y-J
Huang, Y
Wang, L
Guo, X-L
Mi, J-Q
Liu, L-G
Zhu, H
Zhang, Y
Chen, L
Liu, X
Zhang, L-H
Ye, Q-J
Li, B-S
Tang, J-Y
Ford, A
Enver, T
Liu, F
Chen, G-Q
Hong, D-L
Tang, Y-J
Huang, Y
Wang, L
Guo, X-L
Mi, J-Q
Liu, L-G
Zhu, H
Zhang, Y
Chen, L
Liu, X
Zhang, L-H
Ye, Q-J
Li, B-S
Tang, J-Y
Ford, A
Enver, T
Liu, F
Chen, G-Q
Hong, D-L
Document Type
Journal Article
Date
2017-05-01
Date Accepted
2016-09-29
Abstract
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.
Citation
Leukemia, 2017, 31 (5), pp. 1079 - 1086
Source Title
Publisher
Springer Science and Business Media LLC
ISSN
0887-6924
eISSN
1476-5551
Collections
Research Team
Biology of Childhood Leukaemia