Inhibitor binding to topoisomerase II leading to infant leukaemia
This Adverse Outcome Pathway (AOP) describes the linkages between the perturbation
of the normal topoisomerase II enzyme function and infant leukaemia. Infant leukaemia
is a rare haematological disease (1 in 106 newborns, accounting for 10% of all childhood
acute lymphoblastic leukaemias) of developmental origin, manifesting soon after birth
(< 1 year old). The present AOP describes how interference of stressors with DNA topoisomerase
II enzyme can possibly result in DNA double-strand break and chromosomal rearrangement
during intrauterine development and lead to infant leukaemia, manifesting soon after
birth. The proposed AOP is supported by a number of evidences by means of using etoposide
as a model compound to empirically support the linkage between the proposed molecular
initiating event and the adverse outcome. This AOP also identifies several knowledge
gaps, the main ones being the identification of the initiating cell and the investigation
of TopoII poisons in a robust model; thus, the present AOP may be modified in future
on the basis of new evidence. This AOP is referred to as AOP 202 in the Collaborative
Adverse Outcome Pathway Wiki (AOP-Wiki).
Available from December 15, 2022
In series:OECD Series on Adverse Outcome Pathwaysview more titles