Leukemia Research Foundation News

Genetic Mutation Linked to High-Risk Childhood Leukemia

A genetic mutation changing just a few molecules of DNA significantly increases a child’s chance of developing a high-risk subtype of acute lymphoblastic leukemia (ALL), according to a study published in Nature Genetics.

Feng Yue, PhD, a director at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University is a senior co-author of the study. “We discovered how an inherited gene variation regulates multiple known ALL oncogenes,” said Yue. “If we can manipulate this pathway, we could potentially prevent the development of this cancer.”

ALL is the most common leukemia in children. Genetic variations have been linked to ALL previously, but the mutations that lead to subtypes, like the “Ph-like” ALL in this study, have remained mostly uncharacterized.

Dr. Yue and colleagues performed genetic sequencing in more than 5K children with ALL, identifying a genetic variation associated with Ph-like ALL.

Through additional analysis, the researchers linked the mutation to the upregulation of two known cancer-causing genes, CRLF2 and JAK-STAT. These genes are known to promote cell proliferation and growth of cancer — helping explain why the Ph-like subtype is more lethal compared to other forms of ALL.

According to Yue, finding this link will aid in the development of future therapies for ALL and other cancers. “The human genome has 3 billion base pairs, and what we’ve shown here is that one base pair difference can influence this pathogenic pathway — it’s unbelievable,” Yue said. “There are thousands of other genetic variants associated with different human diseases and traits. Such framework could be applied to many other types of cancer, as well.”

Dr. Yue’s research on Ph-like ALL was supported in part by the Leukemia Research Foundation in 2016. Since then, Yue has been awarded several grants to continue this research, including four grants from the National Institutes of Health.


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