Research sheds fresh light on the causes of CLL
Scientists have linked the risk of developing chronic lymphocytic leukemia (CLL) to the inheritance of nine regions of DNA, five of which help white blood cells fight disease.
The research sheds fresh light on the causes of CLL and could lead researchers to new targeted drugs for the disease, or help in selecting existing immunotherapy treatments.
An international team, co-led by scientists at The Institute of Cancer Research in London conducted the largest study of its kind in CLL.
“CLL is essentially a disease of the immune system, and it’s fascinating that so many of the new genetic variants we have uncovered seem to directly affect the behavior of white blood cells and their ability to fight disease.”
These new variants affecting the immune system were each individually associated with an increased risk of up to 17 percent of developing CLL.
Two fell within regions of DNA that have previously been linked with autoimmune disorders — multiple sclerosis and lupus.
“At the moment, CLL is incurable and we desperately need to find new ways to tackle this blood cancer,” said Dr. Alasdair Rankin, Director of Research at Bloodwise. “This important research provides another valuable layer in understanding how genetic variations cause CLL to develop.
“We are beginning to gain a detailed picture of what drives this disease, and we hope this eventually leads to more accurate diagnosis and more informed personalized treatment for people affected by CLL.”
The researchers have now found 41 DNA changes that influence the risk of developing CLL, a slow-growing a cancer of the white blood cells.
The cancerous white blood cells aren’t as good at fighting infection as their healthy counterparts and competing for space with other essential cells such as red blood cells and platelets.
The new study combined data from six previous studies and two new studies involving 6,200 people with CLL.
“We’re increasingly appreciating that part of the key to understanding cancer and how to treat it lies in the immune system,” said Professor Paul Workman, Chief Executive of the ICR. “This fascinating study makes a link between genetic variants in the immune system and the development of leukemia and implicates regions of DNA which are also involved in auto-immune diseases.
“The findings could point us toward new ways of treating leukemia or better ways of using existing treatments — potentially including immunotherapies.”
One of the new variants resides in the gene BANK1, only ever activated in a type of white blood cell called B cells, and linked to the autoimmune disease lupus.
Another was found in the gene ZBTB7A, which regulates B cells numbers — so errors in this gene could lead to too many B cells in the bloodstream and bone marrow.
A third was found in a region of chromosome 22 which has been linked with the risk of developing multiple sclerosis.
Study co-leader Richard Houlston, Professor of Molecular and Population Genetics at the ICR, said: “We knew people were more likely to develop chronic lymphocytic leukemia if someone in their family had suffered from the disease, but our new research takes a big step towards explaining the underlying genetics.
“CLL is essentially a disease of the immune system, and it’s fascinating that so many of the new genetic variants we have uncovered seem to directly affect the behavior of white blood cells and their ability to fight disease.
“Understanding the genetics of CLL can point us towards new treatments for the disease, and help us to use existing targeted drugs more effectively.”