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Study Shows Why Leukemia Returns in Some Children

Published: Thursday, February 28, 2013
Last Updated: Thursday, February 28, 2013
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With sophisticated new DNA techniques, a team of researchers has found, for the first time, why many children with a type of leukemia suffer a relapse.

The researchers found that about 20 percent of children with T-cell acute lymphoblastic leukemia (T-ALL) who experience a relapse harbor mutations that activate NT5C2, an enzyme that inactivates an important chemotherapy drug, 6-mercaptopurine (6-MP).

The discovery may soon lead to improved treatment for patients. “The most immediate thing to do now is to develop diagnostic tools,” said Ferrando, professor of Pediatrics and of Pathology & Cell Biology in the Herbert Irving Comprehensive Cancer Center.

“With diagnostic tools, we could monitor for this mutation and if we see it, these patients should probably receive a different drug.”

About one in five children with T-ALL will suffer a relapse, and despite intensive chemotherapy, most of these children will die from the disease.

Based on his findings, Ferrando said relapsed patients with the mutated enzyme could be switched to a new drug, nelarabine, that’s very similar to 6-MP. The researchers found that even though the two drugs act similarly, they are different chemically, and nelarabine is not affected by the mutated enzyme.

Full findings of the research were published Feb. 3 in Nature Medicine.

The mutated enzyme also was discovered independently in a New York University study of patients with the B-cell form of ALL.

In a New York Genome Center article about both studies, the leader of the NYU study, William Carroll, MD, said

“I think for those of us who treat leukemia, it is a really dramatic finding. Access to [patient] samples and new next-generation sequencing [give us a way] to really understand the blueprint of relapse and to develop specific therapies. We can individualize treatment.”

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