When two independent DNA mutations occur together, they tend to predict severe children leukaemia’s, according to new research reported in JAMA Oncology. The researchers investigated tumor characteristics of more than 1,300 early cancers.

Patients diagnosed with B-cell acute lymphoblastic leukemia, a type of cancer that impacts the white blood cells in the bone marrow, so over a decade of a task in several research sites comprising various continents. This can help the experts decode the disease in the coming days.

Gene Variants For Aggressive Young Leukemia’s Have Been Discovered

 The Leukemia & Lymphoma Society (ALL) is the most frequent type of malignancy in children. This study sheds light on the genetics of this disease in children who have had the worst results, such as relapse and/or death.

Gene Variants For Aggressive Young Leukemia’s Have Been Discovered

The researchers looked for common abnormalities in the DNA of leukemia cells.

“They discovered that a barely visible section of DNA known as 22q11.22 is missing in roughly 30–40% of young B-cell ALL patients,” explains Joshua Schiffman, MD, a co-senior author on the paper. Schiffman is a Huntsman Cancer Institute (HCI) pediatric cancer physician-scientist and a professor of pediatrics at the University of Utah (U of U).

They started to investigate if something so insignificant was absent so frequently and if this missing fragment of DNA had an impact on survival? This is when the researchers switched their focus to IKZF1, a far more well-known gene in juvenile leukemia.

“IKZF1 alterations have perplexed clinicians for a long time,” says Luke Maese, DO, a pediatric oncologist at HCI and an associate professor of pediatrics at the University of Utah who treats leukemia patients at Intermountain Primary Children’s Hospital.

“IKZF1 mutations have been linked to a poor prognosis in some, though not all, patients for over a decade.” The researchers began looking into whether this missing piece of 22q11.22 may be used in conjunction with IKZF1 alterations to better accurately predict results.

“Certainly enough, kids with both the 22q11.22 deletion and the IKZF1 changes—commonly referred to as a ‘double deletion’—had among of the poorest outcomes in pediatric leukemia,” Schiffman says. Patients with an IKZF1 mutation who also had a deletion in the 22q11.22 area had nearly twice the chance of relapse, according to the researchers.

The researchers used advanced genomic analysis tools to look at both hereditary and environmental factors in B-cell ALL malignancies in children. They looked at genomic data from children with cancer from a variety of states and nations.

Patients with Down syndrome who’d been diagnosed with childhood leukemia were enrolled in the study. Leukemia is more common in children with Autism.

David Spencer Mangum, MD, co-lead author and currently an assistant professor of pediatric hematology/oncology at Nemours Children’s Health, recalls working on this project as a medical resident visiting Schiffman’s lab at HCI at most a decade ago. “They never stopped trying to figure out what this 22q11.22 deletion would affect children with leukemia during his years of training. To ensure that this discovery was true and repeatable, they gathered information from a variety of clinical trials “Mangum adds.

“These findings are remarkable because they discovered that the risk of recurrence and death was constant across diverse cohorts of kids with ALL, includes Down syndrome children.”

The researchers believe that this discovery will lead to new therapy options for children with leukemia. The prevalence of the 22q11.22 focal deletion, for example, suggests that it may be relevant for leukemia formation, and its concomitant relationship with poorer outcomes suggests that it could be a helpful clinical diagnostic marker in the future. Children with double deletion leukemia may require further treatment or immediate bone marrow transplantation.