RELAPSE IN PAEDIATRIC ALL PATIENTS DUE TO CHEMOTHERAPY INDUCED MUTATIONS

Edited by, SNEHA MAVIS

Acute lymphoblastic leukaemia (ALL) is one of the most treatable children malignancies due to chemotherapy. Researchers from the U.S., Germany, and China have now demonstrated how chemotherapy drugs known as thiopurines can cause mutations that put patients up for relapse.

This study included ALL samples collected from relapsed paediatric ALL patients in the U.S., China, and Germany. Researchers examined over 1,000 samples obtained from patients at various stages of treatment, including samples from 181 patients gathered at diagnosis, remission, and relapse.

Increased thiopurine-induced mutations were connected to altered genes like MSH2 in leukaemia, according to the study. ALL became resistant to thiopurines after the mutations inactivated a DNA repair pathway known as mismatch repair. A tenfold increase in ALL mutations, including a change in the tumour suppressor gene TP53, was fueled by the combination. Treatment-induced mutations are thought to play a role in 25% of paediatric ALL relapses, according to researchers. The thiopurine-associated mismatch-repair signature was seen in 8% of the participants in this investigation.

The study provides the first direct genomic and experimental evidence in paediatric cancer that drug-resistant mutations can be generated by chemotherapy and are not always present at diagnosis.