Research brings personalised medicine for acute myeloid leukaemia a step closer
Blood Cancer UK scientists at the University of Birmingham have revealed the roles that different types of gene mutations play in causing blood cancers.
The findings, which are the result of over a decade of research, will bring tailored and targeted treatment specific to individual patients one step closer– increasing chances of survival.
The Bloodwise-funded team, led by Professor Constanze Bonifer and Professor Peter Cockerill, has spent the last 10 years carrying out painstaking analysis of cells from people diagnosed with acute myeloid leukaemia (AML).
Identifying what goes wrong in healthy blood cells
AML is an aggressive cancer of white blood cells called myeloid cells, which normally function to fight bacterial infections and eliminate parasites from the body.
By picking apart mutated AML cells from patients, the researchers were able to study the basic building blocks that control the production of these abnormal cells. They were able to identify the main ‘trigger points’ during cancer development where critical mutations influence the working of other genes that control the cells’ identity and behaviour.
The results are published today, 12 November, in Nature Genetics.
Lead author Professor Constanze Bonifer said: “Our research found that 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 to target and develop new drugs to treat each type of AML in a different way.”
Using targeted drugs for individual patients
Co-lead author Professor Peter Cockerill said: “Doctors in Birmingham are already testing AML patients for the many different mutations that cause AML. However, now they know which genes are the most important for each type of AML.
“This means that personalised medicine will one day become a reality for blood cell cancers, which will see a different drug being given to treat each form of AML, creating personalised treatment for each cancer patient depending on the mutation that has caused their disease.”
Dr Alasdair Rankin, Director of Research at Bloodwise, said: “Although a handful of targeted drugs have recently become available for people with acute myeloid leukaemia, they only help a small number of people. We need to be smarter about matching the right treatment to the right person if we want to boost survival rates for AML, especially if there are already drugs out there that can help.
“These landmark research findings will act as a blueprint for how to tackle this and could even help with the delivery of personalised medicine in mainstream healthcare in the future.”
Using a breast cancer drug to treat AML
Further research by the same Bloodwise-funded University of Birmingham team, in collaboration with Professor Olaf Heidenreich’s team at Newcastle University, focussed on just one type of DNA mutation in AML to study a single pathway to cancer development.
The research – published in October in the journal Cancer Cell – found that a growth-promoting gene called ‘CCND2’ was crucial for the survival of this type of cancer cell. Significantly, an existing breast cancer drug called palbociclib, which is designed to inhibit CCDN2, was able to block tumour development.
Identifying patients who are more likely to relapse
Additional research published in the same issue of Cancer Cell by the Birmingham researchers, this time in collaboration with scientists in the Netherlands, looked at how AML treatment can be tailored for patients who are more likely to relapse.
Professor Bonifer explained: “Acute myeloid leukaemia is made up of several groups of cells with different combinations of mutations, some of which are so aggressive they allow these cancer cells to survive after treatment.”
“Often these combinations of mutations are present before treatment, but we have never previously been able to identify them when a patient is first diagnosed with AML - meaning that the cancer can later return as a different disease which is often more aggressive.
“Our research in collaboration with the University of Groningen identified how to makes it possible to identify these cells when patients are first diagnosed with AML so that they can be treated with the right combination of drugs.”
Find our more about the blood cancer research we fund in the Midlands