Chemotherapy has helped make the most common childhood cancer one of the most curable, but researchers have evidence that the treatment may also prime some patients for relapse. Results published in the journal Blood reported that treatment-induced mutations cause drug resistance in some patients whose acute lymphoblastic leukemia (ALL) returns.

“Our study reveals the evolution dynamics of pediatric ALL, which suggest for the first time that chemotherapy treatment, particularly thiopurines, can cause mutations that lead to drug resistance in patients,” said study co-corresponding author Jinghui Zhang, Ph.D., chair of the St. Jude Children’s Research Hospital Department of Computational Biology. Thiopurines are a class of drugs used in most phases of ALL treatment.

The study involved 103 young ALL patients who relapsed. Most relapsed nine or more months after diagnosis. The analysis revealed that about 20% of these patients had treatment-related mutations at relapse, some associated with drug resistance. “The mutational signatures are specific and therapy-related, as they are only present in the genomes of relapsed ALL patients but not in other pediatric or adult cancer genomes,” Zhang said.