Repurposed Drugs Show Promise for Treating Aggressive Infant Leukemia in Preclinical Studies
Key Insights
University of Edinburgh researchers identified three clinically available drugs that demonstrated strong anti-leukemic effects against KMT2A::AFF1 positive B-cell precursor acute lymphoblastic leukemia (search) in mouse models.
Acetazolamide, tacrolimus, and LB-100 significantly reduced disease burden and showed potential to replace or complement harsh chemotherapy regimens currently used for this rare but severe infant leukemia (search).
The study revealed that restoring three microRNA molecules at low levels in this leukemia type could slow cancer cell growth and survival, identifying new therapeutic targets.
University of Edinburgh researchers have identified three clinically available drugs that could provide safer and more effective treatments for one of the most aggressive forms of childhood leukemia (search). The preclinical study, conducted in mice, demonstrated that acetazolamide, tacrolimus, and LB-100 showed strong anti-leukemic effects against KMT2A::AFF1 positive B-cell precursor acute lymphoblastic leukemia (search) (BCP-ALL (search)), a rare but severe form of infant leukemia (search).
Targeting a Rare but Devastating Disease
KMT2A::AFF1 (search) positive BCP-ALL (search) is characterized by rapid disease progression, high risk of relapse, and limited treatment options. While the condition accounts for only a small proportion of childhood leukemia (search) cases, it represents the most common genetic driver of leukemia in infants, occurring in the majority of cases diagnosed under one year of age. Current treatment requires intensive chemotherapy that can improve survival rates but often causes serious toxicities in young patients.
The research team examined three microRNA molecules—miR-194 (search), miR-99b (search), and miR-125a-5p (search)—that are found at unusually low levels in this form of leukemia. When researchers restored these molecules in mice, they observed slowed growth and survival of cancer cells, revealing new therapeutic vulnerabilities.
Drug Repurposing Strategy Yields Promising Results
The scientists identified three genes linked to the disease and discovered that existing drugs could block their activity. The three repurposed candidates included acetazolamide, commonly used for glaucoma and seizures; tacrolimus, prescribed for eczema and psoriasis; and LB-100, an investigational drug used to treat certain brain, lung, and ovarian cancers.
In preclinical studies, all three drugs demonstrated significant anti-leukemic effects, substantially reducing disease burden. Acetazolamide delivered particularly promising results, prolonging survival and improving the effectiveness of standard treatments when used in combination. The drug also showed minimal toxicity in healthy cells, suggesting it could provide a safer alternative or complement to conventional chemotherapy.
Potential to Reduce Treatment Burden
The study suggests that acetazolamide could potentially replace or reduce reliance on cytarabine, a chemotherapy drug known for harsh side effects including hair loss, ulcers, and neurological issues such as aphasia and problems with motor control. This could significantly lessen the treatment burden for young patients while maintaining therapeutic efficacy.
"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," said Katrin Ottersbach, Professor of Developmental Hematology at the University of Edinburgh's Centre for Regenerative Medicine. "We hope our findings may help to improve the treatment outcome and quality of life of these young patients."
Next Steps and Clinical Translation
The research team, which included scientists from the Princess Máxima Center for Pediatric Oncology (search) in The Netherlands, emphasized the need for further studies and clinical trials to confirm the safety and effectiveness of these treatments in patients. The drug repurposing approach could potentially accelerate access to improved therapies while reducing the development timeline compared to novel drug discovery.