New York:
The enzyme that helps create antibodies to fight malaria also causes DNA damage that can lead to a highly aggressive type of blood cancer in children, a new study has claimed.
In equatorial Africa, a region known as "lymphoma belt," children are ten times more likely than in other parts of the world to develop Burkitt's lymphoma, a blood cancer that can be fatal if left untreated, researchers said.
That area is also plagued by high rates of malaria, and scientists have spent the last 50 years trying to understand how the two diseases are connected.
The parasite that causes malaria infects red blood cells and liver cells, while Burkitt's lymphoma originates in infection-fighting white blood cells called B lymphocytes.
Researchers working with mice found that the same enzyme that helps create antibodies that fight the malaria parasite also causes DNA damage that can lead to Burkitt's lymphoma.
"The body needs this enzyme in order to produce potent antibodies to fight malaria. But in the process, the enzyme can cause substantial collateral damage to the cells that produce it, and that can lead to lymphoma," said first author Davide Robbiani, an associate professor at Rockefeller University in US.
In the study, the researchers infected mice with a form of the parasite that causes malaria, Plasmodium chabaudi. They saw that the mice experienced a huge increase in germinal centre (GC) B lymphocytes, the activated form of the white blood cells that can give rise to Burkitt's lymphoma.
As these cells rapidly proliferate, they also express high levels of an enzyme known as activation-induced cytidine deaminase (AID), which induces mutations in their DNA.
As a result, these cells can diversify to generate a wide range of antibodies. But in addition to beneficial mutations in antibody genes, said Robbiani, AID can cause "off-target" damage and shuffling of cancer-causing genes.
Next, the researchers bred mice lacking the p53 gene, which is known to protect cells from many types of cancer, including Burkitt's lymphoma.
In analysing mice that expressed AID but not p53, they found that every single one developed lymphoma.
When these mice were infected with the malaria parasite, they developed lymphomas specifically in mature B cells, similarly to what happens in Burkitt's lymphoma.
"This finding sheds new light on a long-standing mystery of why two seemingly different diseases are associated with each other," said Robbiani.
"If we could somehow limit this collateral damage to cancer-causing genes without reducing the infection-fighting powers of B cells, that could be very useful," he said. The research was published in the journal Cell.