Finding the Path of No Return for Kids with Cancer

Acute lymphoblastic leukemia genetic mutations linked to relapse identified

February 10, 2013 / Author:  / Reviewed by: Robert Carlson, M.D

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(dailyRx News) The cure rate for one type of blood cancer that affects children - acute lymphoblastic leukemia (ALL) – is now about 80 percent. For the remaining 20 percent of kids who develop the disease, the outlook can be dire.

That’s why scientists are scrambling to find ways to manage ALL before it gets out of hand.

Recent research has uncovered genetic mutations that are linked to the vengeful return of ALL. These changes are also associated with cells becoming resistant to treatment medications.

This discovery could one day lead to a way to predict which patients are likely to relapse. Knowing which patients are likely to relapse may allow doctors to adjust initial treatment accordingly.

"Talk to a doctor if your child has frequent or severe nosebleeds."

The new research is the achievement of William L. Carroll, MD, director of NYU Langone Medical Center's Cancer Institute, and colleagues.

"There has been no progress in curing children who relapse, in spite of giving them very high doses of chemotherapy and bone marrow transplants," Dr. Carroll said in a statement.

Dr. Carroll, graduate student Julia Meyer and researchers at five US institutions spent three years examining and analyzing bone marrow samples from 10 pediatric ALL patients. This effort led to the sequencing of 100 billion letters of RNA, the messenger that carries DNA instructions.

Samples were gathered at the time of diagnosis, during remission and after the disease returned (relapsed). Researchers discovered that patients developed between one and six mutations during the course of the disease – from the time it was diagnosed until relapse.

Altogether, 20 mutations related to relapse were identified, none of which had been associated with ALL relapse before.

The team also sequenced the NT5C2 gene gathered from 61 other children who had suffered an ALL relapse. This research pinpointed another five mutations which disrupted the gene’s programming.

This gene seems to play a role in the cancer cells' becoming resistant to chemotherapy. Seven children with altered NT5C2 relapsed within three years.

Dr. Carroll said, "We plan to test the feasibility of screening patients during therapy using sophisticated sequencing technology to pick up low level mutations in NT5C2 and other genes indicating that a mutant clone is growing."

He and his team are working to see if identifying this gene early on could allow doctors to switch therapies. The scientists are also trying to find ways to block these genetic mutations altogether.

This work was published February 5 in Nature Genetics.

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Review Date: 
February 7, 2013
Last Updated:
February 11, 2013