British Society for Haematology. Listening. Learning. Leading British Society for Haematology. Listening. Learning. Leading
29 April 2019

A protein has been identified as a “promising target” for drugs to treat acute myeloid leukaemia (AML).

Researchers have found that the protein YTHDF2 is responsible for triggering and sustaining the disease. What’s more, it is not needed for the functioning of healthy blood cells.

The research was led by scientists at Queen Mary University of London and the University of Edinburgh, working with others at the University of Manchester, Harvard Medical School and the Université de Tours, France.

In the study, published in the journal Cell Stem Cell, blood samples from AML patients showed that YTHDF2 is abundant in leukaemia cells. Experiments in mice, where the Ythdf2 gene was removed from normal and cancerous haematopoietic stem cells, found that the protein is needed to both initiate and maintain disease.

Furthermore, the researchers show in these mouse experiments that the protein is not needed for normal haematopoiesis, and in fact removing Ythdf2 leads to an expansion of normal haematopoietic stem cells.

Professor Kamil Kranc, from Queen Mary, said: “Our work sets the stage for therapeutic targeting of cancer stem cells in leukaemia while enhancing the regenerative capacity of normal blood stem cells. We hope this will establish a new paradigm in cancer treatment.”

Professor Dónal O’Carroll from Edinburgh, who co-led the study with Professor Kranc, said: “The study shows the promise of a novel class of drugs as the basis for cancer and regenerative medicine treatments.”


Source: Paris, J., Morgan, M., Campos, J., Spencer, G.J., Shmakova, A., Ivanova, I., Mapperley, C., Lawson, H., Wotherspoon, D.A., Sepulveda, C., Vukovic, M., Allen, L., Sarapuu, A., Tavosanis, A., Guitart, A.V., Villacreces, A., Much, C., Choe, J., Azar, A., van de Lagemaat, L.N., Vernimmen, D., Nehme, A., Mazurier, F., Somervaille, T.C.P., Gregory, R.I., O’Carroll, D., Kranc, K.R. (2019) “Targeting the RNA m6A reader YTHDF2 selectively compromises cancer stem cells in acute myeloid leukemia”, Cell Stem Cell, available from doi:10.1016/j.stem.2019.03.021

 

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