Liz Burtally
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Leukaemia and the value of junk DNA

Liz Burtally
Posted by
15 Mar 2017

Find out how a hotspot in ‘junk’ DNA appears to be controlling how a nearby cancer-causing gene behaves.

After the human genome project was completed, many people were surprised to learn that 98% of our DNA had no apparent function, as it did not code for any functional genes. These often long, and somewhat mysterious stretches of DNA became known as ‘junk DNA’, and were largely dismissed.

Genetic code. Credit: National Human Genome Research Institute CC BY 2.0.

But research is beginning to show that junk DNA is actually involved in causing cancer in ways we do not yet fully understand. 

In a study supported by Bloodwise, Dr Marc Mansour and his colleague Dr Sunniyat Rahman have identified a hotspot in ‘junk’ DNA that appears to be controlling how a nearby cancer-causing gene behaves.

I caught up with the team to find out how.

The LMO2 gene and T cells

T-cells are special blood cells that fight infections, particularly viruses, when you're not well. Making these special T-cells is no easy task, and whilst nature has learnt how to do this very efficiently, sometimes things go wrong.

A gene called LMO2 is usually switched on to help the body develop and grow T-cells. As the T-cells mature, LMO2 is usually switched off or silenced, as it is no longer needed. Researchers are still finding out how the gene gets switched off as this is needed to stop T-cells growing uncontrollably.

When LMO2 turns bad

When LMO2 is turned back on and left on, it causes T-cells to grow out of control, leading to a very aggressive form of blood cancer called T-cell acute lymphoblastic leukaemia (T-ALL). Researchers know that this loss of control can happen when DNA becomes damaged. But high levels of LMO2 expression is also found almost half of all cases that don’t have the characteristic DNA damage that is associated with T-ALL, so there must be some other mechanisms that is influencing the genes behaviour.

More than junk DNA

Drs Mansour and Rahman recently found new mutations in a junk DNA region next to LMO2 that appear to influence how LMO2 behaves. The mutations introduce binding sites for transcription factors – proteins that turn other genes on and off - which permanently switch on LMO2. When this happens, T-cells start to grow out of control, which ultimately leads to T-ALL.


The LMO2 gene is usually switched off after T-cells mature, as it is no longer needed. When mutations in junk DNA switch on the LMO2 gene, this can lead to T-ALL.

Researchers then used a cutting edge technique called CRISPR, which enables them to edit the genome by turning different genetic targets on or off. They found that if they removed the mutation from the hotspot in the junk DNA using CRISPR, they could return LMO2 to its off state.

Where to next

Dr Mansour says: “T-ALL is a type of acute leukaemia meaning that it is aggressive and progresses quickly. At the moment, treatment options include non-specific chemotherapy or radiotherapy, or a gruelling stem cell transplant. Although significant advances have been made in the treatment of T-ALL, there are still many people who do not respond to their treatment, or are unable to tolerate the side-effects or procedures. So we urgently need to find new ways to treat this aggressive type of blood cancer.”

Dr Rahman tells me: “Our research wants to understand the fundamental biological events that cause T-ALL, so we can help develop new and more precise therapeutic options for people living with this blood cancer. Finding mutations in the ‘junk DNA’ may help highlight new ways to target the genes that drive T-ALL that so far have been under the radar. Working with other international colleagues, we have also discovered similar mutations near other genes known to drive T-ALL, including TAL1 and the closely related LMO1. And now we know that junk DNA can be really important in leukaemia formation, it is likely to also be relevant to other types of cancer.”

What we previously thought was biologically unimportant is now proving to hold insights into how blood cancer develops and how we can treat it. So perhaps ‘junk DNA’ is not so useless after all.

We hope you enjoyed reading our update!

We are very grateful to our supporters for enabling us to carry out exciting research such as this, but we need your support to continue if we are to take this research to the next stage. Find out how you can help.

Find out more about our exciting research here.


The UCL team: From left to right: Michael Magnussen (Research Technician); Sunniyat Rahman (Postdoctoral Scientist); Tanya Rapoz-D’Silva (Research Technician); Theresa León (Postdoctoral Scientist); Nadine Farah (Clinical Research Training Fellow); Dorien Pastoors (Masters Research Student); Marc Mansour (Principal Investigator).



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