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

Research led by St. Jude Children's Research Hospital scientists has linked an inherited gene variation to a nearly four-fold increased risk of developing a pediatric acute lymphoblastic leukemia (ALL) subtype that is associated with a poor outcome. The study appears today in the online edition of the scientific journal Nature Genetics.

The high-risk variant was found in the GATA3 gene. Researchers reported the high-risk version of the gene was more common among Hispanic Americans and other individuals with high Native American ancestry than those of other ethnic backgrounds. Forty percent of Hispanic Americans carried the high-risk variant, compared to 14 percent of individuals of European ancestry. For this study, ethnicity was defined by genetic variations associated with ancestry rather than individual self-reports.

Hispanic children are known to be at a higher risk of developing ALL and of dying from the disease. This is the latest in a series of St. Jude studies to report an association between inherited DNA variations in a handful of genes and an increased risk of childhood ALL among those of Hispanic ethnicity.

This is the first study to link an inherited genetic variation to an elevated risk of developing the leukemia subtype known as Philadelphia chromosome-like ALL (Ph-like ALL). Individuals with the high-risk version of GATA3 were 3.85 times more likely than those who inherited a different version of the gene to develop Ph-like ALL. Patients with the high-risk variant were also more likely to have a poor treatment response and have their cancer eventually return.

A significant percentage of patients with the high-risk GATA3 variant also had the tumor genetic alterationsincluding mutations, gene deletions and chromosomal re-arrangementsthat are hallmark of Ph-like ALL. The changes occur in genes, including CRLF2, JAK and IKZF1 that regulate how blood cells grow and mature.

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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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