Three clinically available drugs could pave the way for safer and more effective treatments for one of the most aggressive forms of childhood leukemia, a new study suggests. 

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

Repurposing these drugs could accelerate access to improved therapies while reducing the serious side effects associated with current chemotherapy regimens, experts say. 

However, the research team from the University of Edinburgh emphasized 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, a high risk of relapse and limited treatment options. Although intensive chemotherapy can improve survival rates, it can cause serious toxicities. 

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

The study examined three tiny 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 weaknesses that could be targeted with treatment. 

The team identified three genes linked to the disease and discovered that existing drugs could block their activity. These included acetazolamide, tacrolimus and LB-100 – medicines already used or under investigation for other conditions. 

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

Acetazolamide delivered particularly promising results, prolonging survival and improving the effectiveness of standard treatments when used alongside them. It also showed minimal toxicity in healthy cells, suggesting it could provide a safer 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 to lessen the treatment burden for young patients. 

We are incredibly proud of this work which has gone from very basic, discovery research into the biology of infant blood cancer all the way to preclinical studies, repurposing drugs that are already available for patients. We hope our findings may help to improve the treatment outcome and quality of life of these young patients.” 

Katrin Ottersbach, Professor of Developmental Hematology, University of Edinburgh’s Centre for Regenerative Medicine

Source:

Journal reference:

Malouf, C., et al. (2026), A microRNA expression signature in infant t(4;11) KMT2A::AFF1+ BCP-ALL uncovers novel therapeutic targets. HemaSphere. DOI: 10.1002/hem3.70353. https://onlinelibrary.wiley.com/doi/10.1002/hem3.70353