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DNA damage signalling from the placenta to foetal blood as a potential mechanism for childhood leukaemia initiation.

TitleDNA damage signalling from the placenta to foetal blood as a potential mechanism for childhood leukaemia initiation.
Publication TypeJournal Article
Year of Publication2019
AuthorsMansell E, Zareian N, Malouf C, Kapeni C, Brown N, Badie C, Baird D, Lane J, Ottersbach K, Blair A, C Case P
JournalSci Rep
Volume9
Issue1
Pagination4370
Date Published2019 Mar 13
ISSN2045-2322
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.

DOI10.1038/s41598-019-39552-0
Alternate JournalSci Rep
PubMed ID30867444
PubMed Central IDPMC6416312
Grant ListRJ5649 / / CHILDREN with CANCER UK /
RJ5649 / / CHILDREN with CANCER UK /
RJ5649 / / CHILDREN with CANCER UK /
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