Blood cancer’s “Achilles’ heel”?

CRM scientists have helped make a breakthrough discovery which could open a door for new treatments for leukaemia.

The new study, published in Cell Stem Cell, has identified a protein in the body that plays a key role in blood cancer.

The protein, known as YTHDF2, has been shown to play a significant role in acute myeloid leukaemia (AML), an aggressive cancer of white blood cells which currently has a very poor survival rate. Experiments revealed that YTHDF2 is needed to trigger and sustain the disease, however it’s not needed for healthy cells to function.

The research team tested blood samples donated by leukaemia patients and found that YTHDF2 is abundant in cancer cells, with additional testing on mice confirming that the protein is required to initiate and maintain the disease. Further testing enabled the researchers to determine the biological pathway by which interfering with the function of YTHDF2 selectively kills the blood cancer cells.

The researchers were also able to demonstrate that YTHDF2 was not needed to support the function of healthy blood stem cells, meaning that the production of normal blood cells would not be affected by the absence of the protein. In fact, blood stem cells were found to be even more active in the absence of YTHDF2. This was an important finding as it paves the way for the development of new treatments which can target cancer stem cells while at the same time enhancing the regenerative capacity of normal blood stem cells.

The study was carried out in collaboration with the University of Manchester, Harvard Medical School and the Université de Tours and was supported by Cancer Research and Wellcome. It was jointly led by the Queen Mary University of London and the University of Edinburgh under the leadership of Professor Kamil Kranc, former CRM group leader and current Clinical Professor of Haematology at Barts Cancer Institute, and Professor Donal O’Carroll, CRM Associate Director. 

The study shows the promise of a novel class of drugs as the basis for cancer and regenerative medicine treatments.

Professor Donal O'Carrol

Professor O’Carroll leads a research group at CRM which explores RNA function in germ and stem cell biology. His research tackles fundamental questions regarding the mammalian germ line from an RNA perspective. This new discovery could establish a new paradigm in cancer treatment, leading to the development of new treatments for leukaemia with significantly less harmful side effects than chemotherapy.

This work was supported by funding from CRUK and Wellcome. Read the full study published in Cell Stem Cell