St. Jude: diagnostic mutations in 183 childhood B-ALL cases linked to subtype-specific relapse risk

Scientists at St. Jude Children's Research Hospital and Seattle Children's Hospital, in collaboration with the Children's Oncology Group, reported that mutations present in the original tumor of children with B-cell acute lymphoblastic leukemia (B-ALL) can be associated with relapse risk. The work was published in Blood on November 2, 2026, according to eurekalert.org. The risk-associated changes differ by leukemia subtype eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.

More than 90% of B-ALL patients survive with modern treatments, but outcomes are worse when the disease returns. B-ALL is already divided into subtypes by the genetic changes that drive the cancer, and this guides therapy. The researchers asked whether additional genetic features could explain relapses and help tailor treatment.

Paired diagnosis and relapse samples

The team compared DNA from diagnosis and relapse samples of 183 pediatric B-ALL cases. The authors describe it as the largest study of its kind, which made subtype-level analysis possible.

"We verified that some tumors are born more resistant to conventional therapy," said corresponding author Xiaotu Ma of the St. Jude Department of Computational Biology. The authors had expected mutations that raise risk across all subtypes. Instead, the data showed that a mutation's significance depends on the other genetic features of the disease eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.

ETV6::RUNX1 and other subtypes

One example is the ETV6::RUNX1 subtype, usually associated with a good prognosis. Within it, patients whose tumors carried a fusion of ETV6 exon 5 with RUNX1 exon 4 had a significantly higher relapse risk than those with ETV6 exon 5 fused to RUNX1 exon 3, the dominant fusion transcript in this subtype. First author Yuan Feng said these patients also relapsed faster. The team also identified genetic markers linked to higher relapse risk in other subtypes.

The genomic comparison also showed that about 3% of cases classified as relapses in this cohort were not a return of the original leukemia. They resembled new cancers, sometimes driven by genetic predisposition or other factors. Co-first author Hanxia Li noted that such patients may not need a high-intensity relapse protocol.

The authors say the findings point to the value of examining mutations present at diagnosis rather than those arising during therapy. Ma said that in the future this may help clinicians prevent relapse before it starts. The study was supported by the National Cancer Institute, the St. Baldrick's Foundation, the Fund for Innovation in Cancer Informatics and ALSAC eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.