19 November 2018

British scientists have identified the roles that different types of gene mutations play in causing acute myeloid leukaemia, it has been announced.

The culmination of ten years’ work has led scientists at the University of Birmingham to say that personalised medicine is getting closer in the care of these patients.

The team, led by Professor Constanze Bonifer and Professor Peter Cockerill from the University’s Institute of Cancer and Genomic Studies, undertook a global analysis of the cells of patients diagnosed with acute myeloid leukaemia (AML).

The study, published last week in the journal Nature Genetics, involved picking apart the mutated cells in AML patients and gathering a wide range of data on each of them. Through this ‘big data’ approach, they were able to identify the main trigger points where critical mutations feed through to other genes that control the cells' identity and behaviour.

The research team included Professor Mike Griffiths and his group at the West Midlands Regional Genetics Laboratory at Birmingham Women's and Children's NHS Foundation Trust,

Professor Bonifer said: "In acute myeloid leukaemia, genes are targeted by mutations that encode either master regulators controlling cell identity or factors transmitting signals through the cell, therefore the normal process of turning genes on or off is defunct.

"Our research found that, when this happens, the cells step sideways from their normal developmental programme and speed out of control.

"Crucially, AML cells from patients with the same types of mutations always take the same route when they head off in the wrong direction. Our analyses of each of the pathways that the cells took when developing into cancer identified key points in the cell that could be used in the future to target and develop new drugs to treat each type of AML in a different way."

Co-lead author Professor Peter Cockerill said the research meant that “personalised medicine will one day become a reality for blood cell cancers”.

Source: Assi, S.A., Imperato, M.R., Coleman, D.J.L., Pickin, A., Potluri, S., Ptasinska, A., Chin, P.S., Blair, H., Cauchy, P., James, S.R., Zacarias-Cabeza, J., Gilding, L.N., Beggs, A., Clokie, S., Loke, J.C., Jenkin, P., Uddin, A., Delwel, R., Richards, S.J., Raghavan, M., Griffiths, M.J., Heidenreich, O., Cockerill, P.N., Bonifer, C. (2018) “Subtype-specific regulatory network rewiring in acute myeloid leukemia”, Nature Genetics, available at doi: 10.1038/s41588-018-0270-1


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