Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin.
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.
Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
T-H
TH
Liu
Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Shanghai Children's Medical Center, SJTU-SM, Shanghai, China.
Y-J
YJ
Tang
Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
Y
Y
Huang
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
L
L
Wang
Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
X-L
XL
Guo
Shanghai Institute of Hematology, Ruijin Hospital, SJTU-SM, Shanghai, China.
J-Q
JQ
Mi
Hematological Department, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
L-G
LG
Liu
Shanghai Cord Blood Bank, Shanghai, China.
H
H
Zhu
Shanghai Cord Blood Bank, Shanghai, China.
Y
Y
Zhang
Shanghai Cord Blood Bank, Shanghai, China.
L
L
Chen
Huangshi Love Health Hospital, Huangshi, China.
X
X
Liu
Huangshi Love Health Hospital, Huangshi, China.
L-H
LH
Zhang
Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
Q-J
QJ
Ye
Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Shanghai Children's Medical Center, SJTU-SM, Shanghai, China.
B-S
BS
Li
Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Shanghai Children's Medical Center, SJTU-SM, Shanghai, China.
J-Y
JY
Tang
Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
A
A
Ford
Stem Cell Laboratory, UCL Cancer Institute, University College London, London, UK.
T
T
Enver
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
F
0000-0003-3228-0943
F
Liu
Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
G-Q
GQ
Chen
Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Department of Pathophysiology and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
D-L
DL
Hong
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000096:biosynthesis; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000378:metabolism; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007938:Leukemia / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute; D051379:Mice; D009687:Nuclear Proteins / Q000032:analysis* / Q000096:biosynthesis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011247:Pregnancy; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C474280:FEV protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors