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.\u00a0<\/p>\n
In research conducted in mice, scientists\u00a0identified\u00a0a trio of existing medicines as promising candidates for treating\u00a0a rare and severe form of infant leukemia caused by a genetic changed called\u00a0KMT2A::AFF1.\u00a0<\/p>\n
Repurposing these drugs could accelerate\u00a0access to\u00a0improved therapies while reducing the serious side effects associated with current chemotherapy regimens, experts say.\u00a0<\/p>\n
However, the research team\u00a0from the University of Edinburgh\u00a0emphasized the need for further studies and clinical trials to confirm the safety and effectiveness of these treatments in patients.\u00a0<\/p>\n
The leukemia \u2013 known as\u00a0KMT2A::AFF1\u00a0positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL)\u00a0\u2013\u00a0is\u00a0characterized by rapid disease progression,\u00a0a high risk\u00a0of relapse and limited treatment options. Although intensive chemotherapy\u00a0can\u00a0improve survival rates, it can cause serious toxicities.\u00a0<\/p>\n
The condition is rare, accounting for a small proportion of childhood\u00a0leukemia\u00a0cases, but it is the most common genetic driver of\u00a0leukemia\u00a0in infants, occurring in\u00a0the majority of\u00a0cases diagnosed under one year of age.\u00a0<\/p>\n
The study examined three tiny molecules, known as microRNAs\u00a0\u2013\u00a0miR-194, miR-99b and miR-125a-5p\u00a0\u2013\u00a0which\u00a0are found at unusually low levels in this form of leukemia. When researchers restored these molecules in\u00a0mice, they slowed the growth and survival of cancer cells, revealing new weaknesses that could be targeted with treatment.\u00a0<\/p>\n
The team\u00a0identified\u00a0three genes linked to the disease and discovered that existing drugs could block their activity. These included acetazolamide,\u00a0tacrolimus\u00a0and LB-100\u00a0\u2013\u00a0medicines\u00a0already used or under investigation for other conditions.\u00a0<\/p>\n
In pre-clinical studies, all three drugs showed strong anti-leukemic\u00a0effects, significantly reducing the burden of disease.\u00a0<\/p>\n
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\u00a0provide\u00a0a safer alternative or complement to conventional chemotherapy.\u00a0<\/p>\n
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.\u00a0<\/p>\n
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\u00a0hope\u00a0our findings may help to improve the treatment outcome and quality of life of these young patients.”\u00a0<\/p>\n
Katrin Ottersbach, Professor of Developmental Hematology, University of Edinburgh’s Centre for Regenerative Medicine<\/p>\n
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