Researchers from the Josep Carreras Leukaemia Research Institute (Barcelona), the Centre for Genomics and Oncological Research (GENyO), and the University of Granada have identified a potential therapeutic target in one of the most aggressive forms of paediatric leukemia. Their findings, published in Blood, suggest that an already approved drug, natalizumab, may enhance treatment outcomes for children with KMT2A-rearranged B-cell acute lymphoblastic leukemia (KMT2A-r B-ALL), a disease associated with poor prognosis and high relapse rates.¹

Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. However, KMT2A-rearranged B-cell ALL represents a particularly aggressive subtype that primarily affects infants and very young children. Patients with this genetic alteration often experience frequent disease relapse and lower survival rates compared with other forms of childhood ALL.²

Current treatment strategies include intensive chemotherapy, hematopoietic stem cell transplantation, and more recently, immunotherapy. While these approaches have improved outcomes for many children with leukemia, they remain less effective in patients with KMT2A-rearranged disease, highlighting the need for new therapeutic options.³

The investigators discovered that communication between two proteins located on the surface of leukemia cells plays an essential role in sustaining leukemia growth and progression. Laboratory experiments demonstrated that disrupting this interaction significantly reduced the ability of leukemia cells to survive and spread. In addition, blocking this pathway increased the effectiveness of conventional anti-leukemia therapies in preclinical models.¹ These findings identify a previously unrecognized biological vulnerability that could be exploited to improve treatment outcomes in patients with high-risk leukemia.

A notable aspect of the study is the use of natalizumab, a monoclonal antibody already licensed for the treatment of autoimmune conditions such as multiple sclerosis and Crohn's disease. Rather than developing a completely new drug, the researchers evaluated whether this existing therapy could interfere with the newly identified leukemia pathway.

In preclinical studies involving patient-derived samples, cultured leukemia cells, and animal models, natalizumab successfully inhibited disease progression and enhanced the response to standard treatments. Because the drug has an established clinical safety profile in other diseases, researchers believe it could potentially be repurposed as an additional therapy for children with high-risk leukemia, pending further investigation.⁴

One of the lead investigator of this study emphasized that identifying the biological mechanisms responsible for aggressive leukemia is essential for designing treatments that are both more effective and less toxic. She noted that the study provides a strong scientific basis for future therapeutic development.

It has been highlighted that the research demonstrates the value of collaboration among research institutions, hospitals, patients, families, and funding organizations in advancing paediatric cancer research.

Although the results are encouraging, the investigators caution that the study remains at the preclinical stage. The experiments were conducted using patient samples, laboratory cell models, and animal studies. Natalizumab has not yet been tested in children with KMT2A-rearranged B-cell ALL, and therefore its safety and therapeutic benefit in this patient population remain unknown.

Clinical trials will be necessary before the drug can be considered for routine treatment of this aggressive leukemia subtype. At present, the findings should be regarded as proof of concept rather than evidence supporting an approved clinical therapy.

References:

1. López-Millán MB, Menéndez P, et al. Targeting leukemic cell surface interactions in KMT2A-rearranged B-cell acute lymphoblastic leukemia. Blood. 2026.

2. Pui CH, Mullighan CG, Evans WE, Relling MV. Acute lymphoblastic leukaemia. The Lancet. 2024;403:2480–2498.

3. Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in Children. New England Journal of Medicine. 2015;373(16):1541–1552.

4. Polman CH, O'Connor PW, Havrdova E, et al. A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis. New England Journal of Medicine. 2006;354(9):899–910.