DNA damage signalling from the placenta to foetal blood as a potential mechanism for childhood leukaemia initiation.
Sci Rep
; 9(1): 4370, 2019 03 13.
Article
in En
| MEDLINE
| ID: mdl-30867444
ABSTRACT
For many diseases with a foetal origin, the cause for the disease initiation remains unknown. Common childhood acute leukaemia is thought to be caused by two hits, the first in utero and the second in childhood in response to infection. The mechanism for the initial DNA damaging event are unknown. Here we have used in vitro, ex vivo and in vivo models to show that a placental barrier will respond to agents that are suspected of initiating childhood leukaemia by releasing factors that cause DNA damage in cord blood and bone marrow cells, including stem cells. We show that DNA damage caused by in utero exposure can reappear postnatally after an immune challenge. Furthermore, both foetal and postnatal DNA damage are prevented by prenatal exposure of the placenta to a mitochondrially-targeted antioxidant. We conclude that the placenta might contribute to the first hit towards leukaemia initiation by bystander-like signalling to foetal haematopoietic cells.
Full text:
1
Database:
MEDLINE
Main subject:
Placenta
/
DNA Damage
/
Leukemia, Myeloid, Acute
/
Signal Transduction
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
/
Newborn
/
Pregnancy
Language:
En
Year:
2019
Type:
Article