“We have used an experimental mouse model that always results in this type of leukaemia. The interesting thing is that, when we added a specific molecular cell program that normally only runs during fetal development to adult mice, 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 study in mice 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 reactivate such a program in human cells,” says Bryder.
This research is a good example of the value of collaboration between research groups. A number of research groups in the Division of Molecular Haematology working at the Biomedical Centre, Lund University, are interested in LIN28 and leukaemia.
“Here, we have researchers who are extremely knowledgeable concerning the LIN28 protein, others who are world-leaders in RNA biology and others who specialise in leukaemia. Together, it makes for a perfect match,” says Bryder.
