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Genetic basis of high-risk childhood cancer points to possible new drug treatment strategy
Date:1/20/2013

linking low hypodiploid ALL to Li-Fraumeni syndrome came when researchers found the same TP53 mutation in two generations of the same family. The father was 31 years old when he was found to have a brain tumor associated with Li-Fraumeni syndrome. His son later developed low hypodiploid ALL.

"Identification of children with low-hypodiploid ALL and inherited TP53 mutations could help expand the use of life-saving cancer screening," said Linda Holmfeldt, Ph.D., a St. Jude postdoctoral fellow. She and Lei Wei, Ph.D., of the St. Jude Department of Computational Biology and formerly of Pathology, are the study's co-first authors. "Screening helps save lives by finding cancers much earlier when the odds of a cure are greatest," Holmfeldt said.

Investigators also reported deletions involving Ikaros gene family members that are rare in other ALL patients. The genes play a role in normal immune system development. The IKZF3 gene, also known as AIOLOS, was deleted in 13 percent of near haploid ALL patients. IKZF3 was deleted in nearly 53 percent of patients with low hypodiploid ALL.

Despite such differences, when researchers tested a variety of compounds against cells from both subtypes growing in the laboratory, they found compounds that targeted the PI3K pathway inhibited proliferation. Researchers are testing the effectiveness of these drugs in mouse models.

The authors are Ernesto Diaz-Flores and Mignon Loh , both of University of California School of Medicine, San Francisco; Michael Walsh , Jinghui Zhang , Debbie Payne-Turner , Michelle Churchman , Shann-Ching Chen , Kelly McCastlain , Jared Becksfort '/>"/>

SOURCE St. Jude Children's Research Hospital
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