Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin.
T-H LiuY-J TangY HuangL WangX-L GuoJ-Q MiL-G LiuH ZhuY ZhangL ChenX LiuL-H ZhangQ-J YeB-S LiJ-Y TangA FordT EnverFeng LiuG-Q ChenD-L HongPublished in: Leukemia (2016)
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.
Keyphrases
- acute myeloid leukemia
- stem cells
- bone marrow
- induced apoptosis
- allogeneic hematopoietic stem cell transplantation
- pregnant women
- cell cycle arrest
- transcription factor
- liver failure
- poor prognosis
- young adults
- gene expression
- signaling pathway
- oxidative stress
- cell death
- small molecule
- binding protein
- mesenchymal stem cells
- single cell
- preterm birth
- hepatitis b virus
- extracorporeal membrane oxygenation
- heat shock protein
- drug induced
- mechanical ventilation
- pregnancy outcomes
- gestational age
- case control
- heat shock
- respiratory failure