06 May 2022

British researchers have discovered interactions between two protein “heavyweights” in cancer, which they say could open up new treatments for people with acute myeloid leukaemia (AML).

A team led by researchers from the University of Sussex, Brighton, have found two major oncoproteins could be working together within leukaemia cells, influencing one another’s signalling activity to promote the survival and growth of AML.

β-catenin is a protein often overproduced in AML cells, which is associated with a poor prognosis. By unravelling the network of other molecules that β-catenin interacts with in leukaemia cells, they discovered that it interacts with Wilms Tumour 1 (WT1). WT1 is known to be mutated in Wilm’s tumour – a childhood kidney cancer – but is also frequently overactive and mutated in AML.

Writing in the journal Haematologica, the team says this is an important development because better understanding of molecular interactions in cancer can open up new pathways for treatment.

Dr Rhys Morgan, lecturer in biomedical science and director of the Sussex Haematology Research Group, said: “We’ve known for a long time that each of these oncoproteins contributes to leukaemia progression but never fully understood how, which has hampered treatment design.

“This study has shown for the first time that these two ‘heavyweights’ in leukaemia physically interact and influence each other’s activity in AML cells.

“The overactivity of a signalling molecule called beta-catenin is well established in AML, but this oncogenic activity is dictated heavily by what other molecules it interacts with in a cancer cell.”

Treatments targeting β-catenin have shown limited success. However, Dr Morgan and his team believe there is potential for the development of treatments that focus on disrupting its interaction with other proteins, including WT1.

Dr Morgan said the next step in the research is to try to understand how the interaction of the two proteins contributes to leukaemia progression, and work with scientists to develop treatments which disrupt this.

Source: Wagstaff M, Tsaponina O, Caalim G, Greenfield H, Milton-Harris L, Mancini EJ, Blair A, Heesom KJ, Tonks A, Darley RL, Roberts SG, Morgan RG. (2022) “Crosstalk between beta-catenin and WT1 signalling activity in acute myeloid leukaemia.” Haematologica, doi: 10.3324/haematol.2021.280294

Link: https://haematologica.org/article/view/haematol.2021.280294

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