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Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin

Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin

Authors :
Yan-jing Tang
T. H. Liu
X. L. Guo
L. H. Zhang
L. Chen
Ying Huang
L. G. Liu
Tariq Enver
Q. J. Ye
Feng Liu
Dengli Hong
Anthony M. Ford
Li Wang
X. Liu
Jingyan Tang
Guo-Qiang Chen
H. Zhu
J. Q. Mi
Benshang Li
Y. Zhang
Source :
Leukemia. 31:1079-1086
Publication Year :
2016
Publisher :
Springer Science and Business Media LLC, 2016.

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.

Details

ISSN :
14765551 and 08876924
Volume :
31
Database :
OpenAIRE
Journal :
Leukemia
Accession number :
edsair.doi.dedup.....700fe46b7613a8678e7faae0c554428e
Full Text :
https://doi.org/10.1038/leu.2016.313