A new study led by researchers at the University of Minnesota Medical School has identified genetic factors that may help explain why African American children are less likely to develop acute lymphoblastic leukemia (ALL) but tend to face worse outcomes when they do. The findings were published today in Nature Communications.
ALL is a blood cancer that begins in the bone marrow. It’s the most common type of cancer in children.
The study showed that genetic variants linked to ALL in other ancestries were also present in African American children, although less common, which may explain their lower overall risk. Additionally, the research team uncovered several new variants unique to African ancestry. Children in this study with ALL who carried one of these new risk variants had a 2.6-fold greater risk of death.
“It’s long been recognized that African American children have a lower incidence of ALL but worse outcomes when they do develop the disease compared to children with other ancestries,” said Logan Spector, Ph.D., professor at the University of Minnesota Medical School and Masonic Cancer Center researcher. “We plan to evaluate these new, African-specific genetic variants to understand how they influence survival from leukemia. We hope that this research can be used to tweak therapy for African American patients and improve their outcome.”
These new variants appear to regulate genes that are important in blood cells. The research team posits that they may have evolved as a defense against diseases such as malaria. They were also associated with specific subtypes of ALL with worse treatment outcomes. These findings show how important it is for genomic studies to include people of many ancestries. The team hopes to use this information to improve survival from ALL in African American children.
“It is fascinating that we identified ALL risk variants that appear to be specific to children of African ancestry, and yet many of them also showed functional activity in experiments that we conducted in relevant cell models that are blind to ancestral background,” said Cindy Im, Ph.D., assistant professor at the University of Minnesota Medical School and Masonic Cancer Center researcher. “I really enjoyed contributing to a project that required collaboration with so many institutions across the country, from the many academic hospitals that provided patient samples, to the Children’s Oncology Group, whose clinical trial programs coordinate the treatment of most children diagnosed with cancer in the U.S.”
The research team is adding more cases and using genetic sequencing to identify even rarer variants. Future research could also benefit children in sub-Saharan Africa, where more than 10,000 are diagnosed with ALL each year.
The study was funded by the National Cancer Institute [R01CA239701] and a Cross-Departmental Research Grant from the Minnesota Masonic Charities.
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