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Some cases of the most common childhood cancer, B-cell acute lymphoblastic leukemia (B-ALL), return after treatment—and genetic changes present from the start may help explain why. Scientists at St. Jude Children's Research Hospital and Seattle Children's Hospital, in collaboration with the Children's Oncology Group, found that mutations in a patient's original tumor can be associated with relapse risk, and that these changes differ by leukemia subtype. The findings, published in Blood, could help researchers better estimate and adjust for relapse risk before treatment begins.

More than 90% of patients with B-ALL survive with modern treatments, but outcomes are worse when the disease returns, indicating a need to prevent relapse. B-ALL is already categorized into subtypes based on the genetic changes that drive the cancer, which help guide treatment. However, the researchers wanted to understand whether additional genetic features could help explain relapses and be used to better tailor therapy.

"We verified that some tumors are born more resistant to conventional therapy," said corresponding author Xiaotu Ma, Ph.D., St. Jude Department of Computational Biology. "By identifying the resistance mutations that are already present in the original tumor, we may also have found a better way to stratify patients into higher-intensity treatments to prevent those relapses from ever occurring."

The researchers uncovered these mutations by comparing the DNA from diagnosis and relapsed samples of 183 pediatric B-ALL cases, the largest study of its kind, enabling subtype-level analysis.

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