The different mutations behind acute myeloid leukaemia

Researchers at the Universities of Birmingham and Newcastle have made a breakthrough in understanding how different genetic mutations cause acute myeloid leukaemia (AML) — one of the most common acute leukaemias in adults. Their study has been published in the journal Cell Reports.

As explained by corresponding author Professor Constanze Bonifer, from the University of Birmingham, “It has been known for a long time that acute myeloid leukaemia is highly heterogeneous, involving different disease-causing genetic mutations.

“This in turn leads to highly variable clinical outcomes, with some patients responding better to certain treatments than others.”

Prior to the current study, the reason for the differences in response to treatment was unknown. Now, the researchers have come together to study the DNA of two types of acute myeloid leukaemia in an effort to explain how clinical prognosis can differ.

“We discovered how two closely related oncogenes — genes which have the potential to cause cancer — differently reprogram blood stem cells in acute myeloid leukaemia and send them spiralling out of control,” Professor Bonife said.

Study co-author Dr Justin Loke, also from the University of Birmingham, explained, “We used state-of-the-art molecular technology that studies all genes within leukaemic cells to investigate why two types of the disease with mutations in the same gene display a completely different clinical profile.

“We showed that the maintenance of the leukaemic state of these two types of acute myeloid leukaemia is dependent on different sets of normal genes, therefore identifying a route to developing tailored and personalised treatments for patients with different cancer-causing mutations in order to specifically target each tumour.”