New insights into fetal development may protect against leukaemia

“We have used an experimental mouse model that always results in this type of leukaemia. The interesting thing is that, when we to adult mice added a specific molecular cell program that normally only runs during fetal development, over half did not develop AML,” says David Bryder, professor of experimental haematology at Lund University.

The fetal program that the researchers used consists of the RNA-binding protein LIN28, the normal function of which is to regulate other genes. LIN28 is usually only expressed during fetal development and disappears shortly after birth.

“AML is the result of various cell mutations. In our research model, we can follow the development from the first mutation until the disease is established, something that is impossible to do in humans. Our mouses study shows that LIN28 has a strong prophylactic effect,” says Mohamed Eldeeb, a doctoral student in Bryder’s research group.

The researchers first examined samples from a large number of patients diagnosed with AML, 98 per cent of whom turned out to have no expression of LIN28 whatsoever. In those who did, the level was very low. To understand more about what happens when LIN28 is activated, the researchers then carried out more in-depth molecular and functional studies using their animal model.

“We could see that, in mice, the molecular fetal cell program protected against disease by colliding with the mechanism that drives AML, which might explain why leukaemia is rare in newborns. Given the robust effect we have demonstrated, it will be interesting to study whether the fetal cell program can be used to prevent disease later in life. That said, one should be aware that it remains to be seen how we can reactive such a program in human cells,” says Bryder.