Targeting two faulty genes could be key in treating blood cancer
Targeting two faulty genes associated with a deadly form of blood cancer could help develop better treatments, scientists have said.
A new study, published in the journal Nature, suggests the mutated genes known as SRSF2 and IDH2 join forces to bring about acute myeloid leukaemia (AML) – an aggressive form of cancer in the white blood cells.
Researchers believe targeting both these genes together instead of focusing on them individually could help develop successful treatments for some patients.
At present, more than 3,000 people are diagnosed with AML each year in the UK, with less than two in 10 people surviving longer than five years.
The team at the University of Manchester, along with scientists at the Memorial Sloan Kettering Cancer Centre in New York, looked at genetic information from around 1,000 AML patients.
They found that SRSF2 – a key gene responsible for maintaining normal blood function – mutated in more than 10% of AML patients.
Half of these SRSF2 genes were also found to carry a faulty version of IDH2 – another gene also playing an important part in blood function.
Despite both SRSF2 and IDH2 being previously linked to blood cancer, the scientists said they found that the faults in both these genes appeared together “more often than expected by chance alone”.
Tests on mice showed that AML spreads more quickly and aggressively if leukaemia cells carry faulty versions of both the genes.
The team found that the two mutated genes work together to disrupt a key process known as RNA splicing – which healthy cells use to make proteins.
One protein in particular, known as INTS3, was found to become inactive following this disruption and the researchers believe this protein to be “directly involved in the change from healthy blood to leukaemia”.
Drugs targeting faulty SRSF2 are currently in early clinical trials in the US while a drug against faulty IDH2 has already been approved by the US’s Food and Drug Administration.
However, the scientists say the findings need to be replicated in human patients to understand more about the role these faulty genes play in spreading cancer.
Dr Daniel Wiseman, from the University of Manchester, who was one of the leading authors of the study, said: “There is a lot of excitement around precision medicines that target specific genetic mutations in cancer cells, but to make this a reality we need to better understand what these mutations do, and importantly how they work together in patients.
“Our research shows one of the first examples of how faults in two very different cancer genes cooperate together and bring about other, unpredicted consequences.
“This helps us better understand the complicated process by which healthy blood cells turn into leukaemia cells.
“It also suggests that sometimes the best way to kill cancer cells might be to target different genetic mutations in combination.”
The research was funded by the charity Bloodwise and the Oglesby Charitable Trust.
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