Key Processes During Fetal Development May Protect Against Leukemia

During the foetal stage, a number of so-called cell programs run that are vital to the development of the foetus. In a study published in Cell Reports, researchers from Lund University demonstrate that one of these foetal programs appears to protect against acute myeloid leukaemia (AML). 

“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 foetal development, over half did not develop AML,” says David Bryder, professor of experimental haematology at Lund University.

The foetal 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 foetal 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 foetal 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 foetal 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. 

Reference: Eldeeb M, Yuan O, Guzzi N, et al. A fetal tumor suppressor axis abrogates MLL-fusion-driven acute myeloid leukemia. Cell Rep. 2023;42(2). doi: 10.1016/j.celrep.2023.112099

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