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Chart on ALL

Srushti Shah/Medill

Prevalence of ALL is highest in children aged 2-3, about 66 percent of the total prevalence of ALL in children below 20 years, according to the Centers for Disease Control and Prevention.

Researchers uncover genetic clues to prevent cancer relapse

by Srushti Shah
Feb 20, 2013

A relapse in cancer is worse than the original cancer itself. But researchers have found a way to deal with this, too.

New York researchers have identified mutations in the genes that link to relapse in acute lymphoblastic leukemia in children.

“There has been no progress in curing children who relapse, in spite of giving chemotherapy and bone marrow transplants,” said Dr. William Carroll, of NYU Langone Medical Center’s Cancer Institute, who specializes in pediatric hematology and oncology. Carroll co-lead a study that uncovered mutations linked to the relapse of this childhood leukemia, abbreviated as ALL, which was published in the journal Nature Genetics Feb. 3, 2013.

Every year there are about 3,000 children diagnosed with ALL in the U.S. Out of these, 85 percent survive, while 20 percent have relapse, of which a few survive.

In ALL, the body’s bone marrow produces large number of lymphocytes, or white blood cells. Modern medicine does help to cure the majority of patients, but the difficulty is with the children who have a relapse.

Hence it becomes important to understand the cause of the relapse. The researchers have found mutations in one particular gene that appears to be the cause of relapse in some patients.

“Because of these mutations in the gene, the body develops a resistance to one particular drug that is an important part of treatment,” Carroll said. “So if we could detect these early signs of relapse, the patient could be switched to multiple drugs, which might help the patient to survive the relapse.”

Dr. Nobuko Hijiya, an associate professor of pediatrics at the Feinberg School of Medicine at Northwestern University, said that this would be a major discovery if only treating one gene were the solution to relapse. “The genetic pathway is a complex pathway, and with eradication of one gene, the problem might not be cured,” she said.

Hijiya said that though the study was relevant, it would definitely need more investigation before it could have any clinical implications.

For the study the researchers compared the RNA (large biological molecules that perform multiple vital roles in the coding, decoding, regulation ad expression of genes) at diagnosis and relapse in 10 children with ALL.

Carroll said that they were able to observe these mutations not only at the diagnosis, but also at the relapse, which allowed these leukemia cells to grow in spite of receiving chemotherapy, while the rest of the cancerous cells were killed.

The team extensively studied the RNA sequencing and found about 20 relapse-specific mutations. But two patients showed the mutations in the same gene, NT5C2, which can create resistance to drugs analogous to the ones used in ALL therapy. They analyzed a larger number of samples and detected this mutation in 15 percent of patients who relapsed early in treatment.

Carroll said that this new knowledge might help the doctors to treat relapse in a better way. “If we could detect these cells early we could use to switch the patients to rotational drugs and deal in a better way with the resistant cells.”