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Gene Governs Response to Leukemia Chemotherapy

Acute lymphoblastic leukemia is most common pediatric cancer

WEDNESDAY, Jan. 7 (HealthDay News) -- A mutation in leukemia cells predicts which children with acute lymphoblastic leukemia are more likely to relapse.

The discovery, reported online Jan. 7 in the New England Journal of Medicine, might lead to tests to help physicians fine-tune treatment for different subsets of patients.

"The treatment of acute lymphoblastic leukemia (ALL) is really one of the success stories in American and international medicine in that close to 80 percent of patients can be cured with an intensive and prolonged chemotherapy regimen," said Dr. Arthur Frankel, a professor of medicine at the Texas A&M Health Science Center College of Medicine, who was not involved with the study.

"Having said that," Frankel added, "there are two changes that would improve the quality of care and maybe improve quality of life and the cure rate. One is that you'd like to identify patients that don't need this two years of aggressive chemotherapy. At the same time, there is a need for identifying early those children and adults that would do very poorly and trying to come up with new treatments."

ALL, or cancer of white blood cells called leukocytes, is the most common pediatric cancer.

Although current therapies are effective in a majority of pediatric patients, they can be hard to endure. And still, about 20 percent of patients will relapse, and only about a third of those who relapse will survive beyond five years.

Scientists have already identified a number of genetic mutations and deletions in genes (including the one that's the subject of the new report, IKAROS) that regulate the normal development of leukocytes, said study senior author Dr. James R. Downing, scientific director of St. Jude Children's Research Hospital, in Memphis, Tenn.

"But in prior studies, we never really saw any association with outcome," Downing said.

Downing and his colleagues conducted gene analyses of 221 children with high-risk ALL who were being treated for the disease as part of another study.

Deletions or changes in the IKAROS gene (of which there were several) that were found in slightly more than one-quarter of the patients were associated with a worse outcome. The findings were validated in a second group of 258 children.

IKAROS produces the IKAROS protein, which is involved in regulating other genes.

"The mutations of IKAROS were shown to be independent prognostic indicators, they had high value to identify patients at high risk of relapse over and above known risk factors," Downing said. "Identification of these lesions at the time of diagnosis would provide new information to better identify those patients."

It's unknown how the gene works at this point, but Downing speculated that it has to do with the gene's role in regulating the formation of lymphocyte cells.

Diagnostic tests need to be developed before the study results -- which also need to be replicated -- can be of benefit to patients, the researchers said.

There's another potential benefit down the road: new information to help find new targets for drugs.

More information

Visit the U.S. National Cancer Institute for more on ALL in children.

SOURCES: James R. Downing, M.D., scientific director, St. Jude Children's Research Hospital, Memphis, Tenn.; Arthur Frankel, M.D., professor, medicine, Texas A&M Health Science Center College of Medicine, and director, Cancer Center, Cancer Research Institute and Division of Hematology/Oncology, Scott & White Hospital, Jan. 7, 2009, New England Journal of Medicine, online

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