New Pediatric Cancer Study Focuses on Possible Genetic Risk Factors for Acute Lymphoblastic Leukemia

Although it is one of the most commonly diagnosed pediatric cancers, the survival rates of children with acute lymphoblastic leukemia (ALL) continue to rise. The cancer affects either the B-cells or T-cells in the immune system, crowding a child’s bone marrow and preventing it from making enough healthy immune cells. Thankfully, chemotherapy and stem cell transplants can treat and cure most children within a few years.

Yet, researchers at the University of Minnesota Medical School still see an area of mystery with B-cell ALL. To find answers, the National Cancer Institute funded a study, led by Logan Spector, PhD, a professor in the Department of Pediatrics and member of the U of M Masonic Cancer Center, with a five-year, $3 million grant, called the “Admixture and Risk of Acute Lymphoblastic Leukemia.”

“It has long been known that Black children have half the incidence rate or less of B-cell ALL than white children. At the same time, when Black children are diagnosed with B-cell ALL, they tend to present with worse forms of disease — for instance a higher white blood cell count — and they have lower survival rates than white children,” he said. “There aren’t a lot of scientists who have tried to understand why that might be, and we have built the case that it is likely due to genetics.”

Genetic admixture, Dr. Spector says, is a term used for the genomes of people whose ancestry includes previously isolated populations that have bred together over many generations.

“When this happens, you have genomes that are kind of chopped up and come from different ancestries,” he said. “On average, African Americans are 20% European, and many others have used this data to figure out, for instance, why Black men have twice the rate for prostate cancer as white men. We’re using much of the same statistical techniques but instead applying them to pediatric leukemia.”

To see if genetic admixture plays a role in the disparities of B-cell ALL incidence and outcomes, Dr. Spector will lead a team, including researchers from the Baylor College of Medicine, Yale University and St. Jude Children’s Research Hospital, to begin genotyping hundreds of pediatric patients with B-cell ALL and check for patterns.

“We are working with the Children’s Oncology Group, which is the clinical trials group that treats most children with cancer in the U.S., to obtain 1,500 samples, and then we’ll send those to the U of M Genomics Center to be genotyped,” Dr. Spector said. “We’ll look at each segment to see which ancestry it comes from, and then ‘stack’ them on top of each other to see — do they all happen to have one ancestry or the other at a particular gene, and if so, can we put a statistical value on that? Genes that are disproportionately from one continental ancestry or the other could be responsible for lower risk or worse outcomes.”

Depending on the answers to those questions, Dr. Spector says his team’s research could lead to tailored cancer therapies, possibly even prevention strategies, that impact all children with B-cell ALL.

“Should we find that genes that interact with ALL therapy and lead to worse outcomes for Black children, then we can start doing studies to adjust the dose of these genes to be more appropriate,” he said. “That is our hope — that we will identify potential genetic causes for higher relapse and worse survival rates and be able to intervene by changing dosage.”

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