The research team identified three genes associated with a rare form of childhood leukemia and found that clinically available drugs positively affected these genes in tests on mice, increasing survival rates.
KMT2A::AFF1-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a rare but severe infantile leukemia caused by alterations in the KMT2A::AFF1 gene. BCP-ALL is characterized by rapid disease progression, high risk of recurrence, and limited treatment options, and likewise requires aggressive chemotherapy, which can result in severe side effects.
BCP-ALL is also the most common genetic cause of leukemia in infants, occurring in the majority of cases diagnosed in children under 1 year of age.
Acetazolamide and tacrolimus may be an alternative to powerful chemotherapy drugs
However, research from the University of Edinburgh shows that there is hope for the development of more effective treatments. A study in mice showed that three microRNA molecules (miR-194, miR-99b, and miR-125a-5p) found at abnormally low levels in BCP-ALL patients were restored, resulting in a delay in cancer cell proliferation and survival.
Three genes associated with this particular form of leukemia were found to be affected by existing clinical drugs that can block the genes’ activity. These include 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 showed strong antileukemic effects and significantly reduced disease burden.
The research team, which also included scientists from the Princess Máxima Pediatric Oncology Center in the Netherlands, strongly emphasized the need for further research and clinical trials to confirm the safety and effectiveness of these treatments in patients.
Reducing the burden of cancer treatment for young patients
Acetazolamide therefore has the potential to replace or reduce dependence on cytarabine, a chemotherapy drug with harsh side effects including hair loss, ulcers, and neurological problems such as aphasia and motor control problems.
Katrin Ottersbach, Professor of Developmental Hematology at the University of Edinburgh’s Center for Regenerative Medicine, said: “We are very proud of this work, which goes from very basic discovery work into the biology of infant blood cancers to preclinical work that repurposes drugs already available to patients. We hope that our discoveries will help improve treatment outcomes and quality of life for these young patients.”
The study was published in the journal HemaSphere. This project was funded by the Kay Kendall Leukemia Foundation, Cancer Research UK, the Dutch Cancer Society and the Fight Kids Cancer Fund programme.
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