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Inherited gene variation tied to high-risk pediatric leukemia and greater risk of relapse
Date:10/20/2013

le was known about why a child develops a specific subtype of ALL in the first place and whether inherited genetic variations that predispose an individual to a subtype also influence how he or she responds to the therapy," said corresponding author Jun J. Yang, Ph.D., an assistant member of the St. Jude Department of Pharmaceutical Sciences. "In this study, we discovered a genetic basis for susceptibility to Ph-like ALL, but even more importantly, the evidence that host and tumor genomes may interact with each other to influence the risk of developing and surviving ALL."

The study was done in collaboration with the Children's Oncology Group, a U.S.-based research cooperative study group focused on childhood cancer research and clinical trials. The research included 680 patients enrolled in COG clinical trials.

Ph-like ALL accounts for as much as 15 percent of childhood ALL and is associated with a high risk of relapse and a poor outcome. ALL is the most common childhood cancer. While overall cure rates for pediatric ALL are now about 90 percent, only 63 percent of children with Ph-like ALL are alive and cancer free after five years. Yang added that larger population studies are needed to assess risks associated with these inherited variations.

GATA3 carries instructions for assembling a protein called a transcription factor that turns other genes on and off. The GATA3 protein, and other members of the GATA gene family, plays a crucial role in normal development of a variety of blood cells. Alterations in GATA3 have been linked to other blood cancers, including Hodgkin lymphoma.

The high-risk GATA3 variation was identified using a library of 718,890 common genetic variations known as single nucleotide polymorphisms, or SNPs, to screen the DNA of 75 children with Ph-like ALL, 436 children with other ALL subtypes and 6,661 individuals without ALL. Fifty-eight percent of patients with Ph-like ALL carried the high-risk version of the
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Contact: Summer Freeman
media@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert  

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