Genetic Mutations May Play Role in Some Childhood Leukemias

There could be a new breakthrough on childhood leukemia that could help with better, less punishing treatments in the future. Children that have particular gene mutations are at an increased risk of developing leukemia, according to the first studies to show that genetic inheritance can play a role in developing the disease.

Research into the development of acute lymphoblastic leukemia, also known as ALL, is the most common childhood cancer, suggests that the individuals who inherit specific genetic variants are approximately twice as likely to develop the disease. The findings, which come from the first complete genome search for possible inherited risk factors for ALL, also offer some potential advances in treatment with the identification of a gene that could help predict drug response with the disease. Two studies that have been published in the journal Nature Genetics confirm that alterations in the 1KZF1 and ARID5b genes are linked to the development of ALL, which accounts for approximately 80 percent of leukemia cases in kids.

Scientists have described these findings as a significant advance in helping us understand leukemia. While ALL does  not appear to run in families as some other common genetic diseases, the scientists have established that inherited risk factors are also involved in its development. Most cancers are though to be triggered by a certain combination of factors, which include exposure to the environment, inherited genetic susceptibility, and chance.

Researchers, from the Institute of Cancer Research in Sutton, southwest London, identified inherited variations in genes that control the development of lymphocytes, which are white blood cells that play a very important role in the body’s defenses, by comparing the whole DNA genome of approximately 1,000 British kids that suffered from ALL against the children that did not have the disease. The scientists said that these mutations, individually, could increase the risk of developing All by approximately 30 to 60 percent.

The second study, which was done by a team at St. Jude Children’s Research Hospital in Tennessee, identified the same variant genes from genome scans of 441 children that suffered from the disease. Although adults can also develop this kind of leukemia, it is much more common in children ages 2 to 5, which accounts for about 400 pediatric cases in Britain annually.

Professor Richard Houlston, who is the head of the Sutton Institute’s Molecular and Population Genetic Team, said that the genes encode proteins that are involved in the development of white blood cells that are called B-cells, which produce antibodies to help fight disease and are most commonly affected in ALL. “These findings provide the first evidence that genetic make-up plays a major role in the risk of ALL,” he stated.

Professor Mel Greaves, who is a leukemia biologist and chairman of the institute’s section of haemato-oncology , described the work as “a very significant advance” in helping us understand the complex process in which children develop leukemia. He also added that it should not be taken to mean that children can develop the disease just because of an accident of inheritance. He said, “Genetic risk factors are just one component of the cause. Finding the triggering exposures still remains a focus of intense effort, particularly with respect to possible future prevention.”

Mary Relling, who is the lead author of the American study, said that the ARID5B gene was important in embryonic development and the IKZF1 gene was critical for the development of lymphoid cells, which are cells that are found in the lymph nodes. She also added that even with the genetic mutations, the risk of developing ALL remained at a low rate. “Like all cancers, pediatric ALL is a multifactor disease. But these findings may give us a handle on the mechanism of the disease and drug responsiveness to it.”

David Grant, who is the scientific director at Leukemia Research, which funded the British study, stated, “A complete understanding of how leukemia develops will lead to new, less punishing, treatments to cure all children with this cruel cancer.”