Understanding how the ‘cut-and-run’ genetic fault can cause blood cancer

Lead researcher - Dr Joan Boyes, University of Leeds
Cut-and-run: A new mechanism by which V(D)J recombination triggers lymphoid cancers
Amount awarded: £232,961
Award start date: 19 Sep 2016
Award duration: 3 years

Antibodies are produced by the white blood cells (lymphocytes) in our immune system to fight intruders, such as viruses, bacteria and parasites, and to destroy cancer cells.

The immune system must generate millions of different types of antibodies every day to ensure that the body can fight off the numerous intruders it encounters. To meet this demand, white blood cells can reshuffle their DNA to produce unique antibodies.

Dr Joan Boyes and her team at the University of Leeds have found that many chromosome changes in people with acute lymphoblastic leukaemia (ALL) appear to come from mistakes made by an enzyme that cuts the DNA during the antibody gene production. The enzyme ends up binding with another DNA fragment left over from the cutting process, and the new complex randomly starts making cuts to other parts of the DNA. They have called this faulty mechanism ‘cut-and-run’.

The researchers will investigate how cut-and-run works and aim to find a way to stop the mechanism as a means of treating lymphoid blood cancers, such as ALL.