Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin.
Date
2017-05-01ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Hematopoietic Stem Cells
Cells, Cultured
Animals
Humans
Mice
Leukemia
Fetal Diseases
DNA-Binding Proteins
Nuclear Proteins
Transcription Factors
Gene Expression
Pregnancy
Female
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Heterografts
Research team
Biology of Childhood Leukaemia
Language
eng
Date accepted
2016-09-29
License start date
2017-05
Citation
Leukemia, 2017, 31 (5), pp. 1079 - 1086
Publisher
Springer Science and Business Media LLC