Repurposed drugs could provide safe treatment for aggressive childhood leukemia

A new study suggests that three clinically available drugs could pave the way to safer and more effective treatments for one of the most aggressive forms of childhood leukemia.

In research conducted on mice, scientists identified a trio of existing drugs as promising candidates for treating a rare and severe form of infant leukemia caused by a genetic mutation called KMT2A::AFF1.

Experts say repurposing these drugs could speed access to better treatments while reducing the serious side effects associated with existing chemotherapy.

However, the research team from the University of Edinburgh stressed the need for further studies and clinical trials to confirm the safety and effectiveness of these treatments in patients.

The leukemia – known as KMT2A::AFF1-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) – is characterized by rapid disease progression, high risk of relapse, and limited treatment options. Although intensive chemotherapy can improve survival rates, it can cause severe toxicity.

This condition is rare, accounting for a small proportion of childhood leukemia cases, but it is the most common genetic driver of leukemia in infants, with the majority of cases diagnosed under one year of age.

The study examined three small molecules, known as microRNAs – miR-194, miR-99b and miR-125a-5p – which are found at unusually low levels in this form of leukemia. When researchers restored these molecules in mice, they slowed the growth and survival of cancer cells, revealing new vulnerabilities that could be targeted with treatment.

The team identified three genes associated with the disease and found that existing drugs could block their activity. These include acetazolamide, tacrolimus, and LB-100 – drugs that are already used or are under investigation for other conditions.

In pre-clinical studies, all three drugs showed strong anti-leukemic effects, significantly reducing the burden of the disease.

Acetazolamide gave particularly promising results, prolonging survival and improving the effectiveness of standard treatments when used along with them. It also showed minimal toxicity in healthy cells, suggesting that it could provide a safe alternative or complement to conventional chemotherapy.

The study also suggests that acetazolamide could potentially replace or reduce reliance on cytarabine, a chemotherapy drug known for its harsh side effects, helping ease the treatment burden for young patients.

We are incredibly proud of this work that advances the biology of pediatric blood cancers, from very basic, discovery research to preclinical studies, repurposing drugs that are already available to patients. We hope that our findings can help improve treatment outcomes and quality of life for these young patients.”

Katrin Ottersbach, Professor of Developmental Hematology, Center for Regenerative Medicine, University of Edinburgh