How a protein found in foetal development can prevent acute leukaemia

How a protein found in foetal development can prevent acute leukaemia
© shutterstock/Alexa Mat

Researchers have identified a protein present in foetal development that has a strong prophylactic effect against acute myeloid leukaemia (AML). 

During the foetal stage of pregnancy, several vital “cell programmes” are active in foetal development. According to new research from Lund University in Sweden, one of these foetal programmes can protect against AML. 

The full findings of the study, titled ‘A foetal tumour suppressor axis abrogates MLL-fusion-driven acute myeloid leukaemia’, are published in the journal Cell Reports. 

What is AML?

AML is a cancer of white blood cells. Acute leukaemia describes cancer that progresses quickly and aggressively and usually requires urgent treatment. AML is classified according to the type of white blood cells affected. The two main types of white blood cells are: monocytes and granulocytes, which come from myeloid stem cells and lymphocytes, which originate in lymphoid stem cells 

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

The foetal programme that the researchers used consisted of the RNA-binding protein LIN28. The main function of this protein is to regulate other genes. LIN28 is typically expressed in 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 mouse study shows that LIN28 has a strong prophylactic effect,” said Mohamed Eldeeb, a doctoral student in Bryder’s research group. 

The foetal development programme could help treat leukaemia in adults

The researchers initially examined samples from a large pool of patients diagnosed with AML. In total, 98% of these patients had no expression of LIN28. Even in those who did, the levels of expression were very low. The researchers carried out more in-depth molecular and functional studies in the mice model to understand more about what happens when LIN28 is activated. 

“We could see that, in mice, the molecular foetal cell programme protected against disease by colliding with the mechanism that drives AML. This 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 programme can be used to prevent disease later in life,” said Bryder.

“That said, one should be aware that it remains to be seen how we can reactive such a programme in human cells,” he concluded. 


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