Repurposed drugs could improve treatment for rare infant leukaemia

The Shift Toward Precision Medicine in Infant Leukaemia

For years, the treatment of infant leukaemia has been a battle of attrition. When dealing with KMT2A::AFF1 positive B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), clinicians have historically relied on aggressive chemotherapy. While necessary, these treatments often come with a heavy price—severe side effects that can impact a child’s development and quality of life.

However, a new era of precision medicine is emerging. The goal is no longer just to kill cancer cells, but to do so by targeting the specific genetic drivers of the disease. Recent research from the University of Edinburgh and the Princess Máxima Center for Pediatric Oncology is pivoting the conversation toward targeted interventions that could potentially reduce the reliance on toxic chemotherapy.

Moving Beyond Aggressive Chemotherapy

BCP-ALL is a rare but severe form of leukaemia caused by changes in the KMT2A::AFF1 gene. It is particularly aggressive, characterized by rapid disease progression and a high risk of relapse. Because of this, the standard of care has long been intense chemotherapy.

The challenge is that these drugs are often “blunt instruments.” For example, cytarabine is a powerful chemotherapy agent, but it is associated with harsh side effects including hair loss, ulcers, and neurological complications such as aphasia and impaired motor control. The trend in pediatric oncology is now moving toward finding alternatives that maintain efficacy while sparing the patient from these debilitating effects.

The Power of Drug Repurposing: New Hope from Old Medicines

One of the most exciting trends in modern medicine is “drug repurposing”—taking a drug already approved for one condition and discovering it can treat another. This pathway is significantly faster and safer than developing a new molecule from scratch because the safety profiles are already well-understood.

In pre-clinical mouse studies, researchers identified three existing clinical drugs that showed strong anti-leukaemic effects by blocking specific gene activity linked to BCP-ALL:

• Acetazolamide: Traditionally used to treat glaucoma and seizures, this drug is being explored as a potential replacement or supplement to reduce the dose of cytarabine.
• Tacrolimus: A medication commonly prescribed for psoriasis and eczema.
• LB-100: An investigational drug currently used to treat specific cancers of the lung, brain, and ovaries.

By reducing the “burden of disease” in these tests, these drugs suggest a future where a cocktail of repurposed, less toxic medications could replace the scorched-earth approach of traditional chemotherapy.

Targeting the Genetic Blueprint: The Role of microRNA

Beyond repurposing drugs, scientists are looking deeper into the cellular machinery of cancer. A key focus is microRNA—tiny molecules that aid regulate gene expression. In patients with BCP-ALL, certain microRNA molecules are found at unusually low levels, which may allow the cancer to grow unchecked.

Restoring the Body’s Natural Defenses

Research has identified three specific microRNA molecules—miR-194, miR-99b, and miR-125a-5p—that are depleted in BCP-ALL sufferers. In laboratory tests, restoring these molecules led to slowed growth and decreased survival of cancer cells.

This suggests a future trend where “replacement therapies” could be used to restore the body’s own regulatory mechanisms to suppress tumour growth. As Katrin Ottersbach, Professor of Developmental Haematology at the University of Edinburgh’s Centre for Regenerative Medicine, notes, this perform represents a journey from basic biology to preclinical studies, with the ultimate goal of improving both the treatment outcome and the quality of life for young patients.

Improving Quality of Life for Pediatric Patients

The ultimate metric of success in pediatric oncology is no longer just survival, but survival with quality. The ability to avoid neurological issues like aphasia or the physical trauma of severe ulcers is paramount for an infant’s development.

The collaboration between the University of Edinburgh and the Princess Máxima Center for Pediatric Oncology highlights a growing trend of international, multi-center research. By pooling resources and expertise, these institutions are accelerating the transition from the lab to the clinic. While the research team emphasizes that further clinical trials are essential to confirm safety and effectiveness in humans, the trajectory is clear: the future of infant leukaemia treatment is targeted, personalized, and gentler.

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