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

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

Research Team

Biology of Childhood Leukaemia

Notes