Genetic Testing May Shift Focus in Treating Pediatric Leukemia


Why do some pediatric ALL survivors live the rest of their lives cancer-free, while others face secondary cancers or death?

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in pediatric patients, and while some children with the disease eventually enter remission and live the rest of their lives cancer-free, others unfortunately end up with a secondary cancer diagnosis down the line.

Therefore, researchers at St. Jude Children’s Research Hospital set out to investigate why.

“When you give these patients the same medication, although they all have ALL, their response can vary quite a bit. Some will be cured, some will relapse, some will have severe side effects to therapy,” Jun J. Yang, Ph.D., author on the study and associate member of the Department of Pharmaceutical Science and Department of Oncology at St. Jude, said in an interview with CURE.

The researchers sequenced the DNA of more than 4,000 children with ALL across the country. Specifically, they looked at the 0.7 percent of the population who had a mutation in the TP53 gene.

“This is a very well-known tumor suppressor gene, and it is also known as the ‘guardian of the genome,’” Yang said, explaining that TP53 is responsible for fixing any errors that might occur in a person’s genes.

When TP53 is not working correctly, it can pave the way for cancer growth. In fact, patients with the mutation are about four times more likely to die of their cancer, and about one in four will develop a second cancer.

“It’s very unfortunate that they have a high risk of developing leukemia in the first place and that they are at higher risk of death or getting another cancer. It speaks volumes to the importance of this particular gene,” Yang said. “It’s like a triple-whammy for patients with this germline mutation. We need to work hard to find solutions.”

And while this rare genetic mutation may play a monumental role in a patient’s prognosis, it is not routine for children diagnosed to be tested for it — or any other genetic mutation for that matter. Currently, pediatric ALL is not considered hereditary, so when a child is diagnosed, they usually are not tested and do not have family cancer history gathered, either.

Yang wants to change this — and research like this is helping to shift the momentum in that direction.

“More and more pediatric oncologists, and even parents, are becoming aware of the genetic basis for childhood cancer,” he said. “There is increasing appreciation of the genetic basis for pediatric cancer risk. Moving forward five or 10 years, there needs to be a more standard way of testing patients, particularly children, with cancer.”

Currently, if a child with ALL does undergo genetic testing and is positive for the mutation, there are steps that can be taken. For example, they should have more frequent MRIs to test for other malignancies. Also, it might be a good idea to change the patient’s treatment plan, as certain therapies, such as total body radiation, can lead to secondary tumors.

Yang is confident that treatment improvements will continue to be made for this population.

“This is an emerging field and we are really seeing the tip of the iceberg,” he said. “We have a long way to go, but I’m very excited about cancer predisposition, especially genetic disposition. There will be a lot more biology to be learned that can change the way we’re treating childhood cancer.”

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