Researchers identify a therapeutic vulnerability in aggressive childhood cancers

A team from the Josep Carreras Leukaemia Research Institute has identified a new therapeutic vulnerability in one of the highest-risk subtypes of childhood B-cell acute lymphoblastic leukemia (B-ALL). The findings could pave the way for the development of more effective and personalized treatments for patients who respond poorly to current therapies.

The research focuses on pro-B acute lymphoblastic leukemia carrying the t(4;11) chromosomal translocation, a particularly aggressive form of the disease that primarily affects infants. Although childhood acute lymphoblastic leukemia generally has high survival rates, around one in ten cases carries this genetic alteration, which is associated with a high risk of relapse and an overall survival rate below 40%.

The study shows that these leukemic cells exhibit reduced levels of the HDAC7 protein, a key regulator of normal B-cell development. The researchers found that restoring HDAC7 expression through a combination of the drugs MI-538 and chidamide, together with conventional chemotherapy, promotes the maturation of leukemic cells, reduces their proliferative capacity, and increases their sensitivity to glucocorticoids, one of the cornerstones of treatment for this disease.

The findings, obtained using cellular models, mouse models, and patient-derived samples, also demonstrate that this therapeutic strategy can delay disease relapse and reduce the ability of leukemic cells to re-establish the disease, making it a promising approach for future precision medicine strategies.

This work represents an important step forward in understanding the molecular mechanisms driving high-risk childhood leukemias and opens new avenues for the development of targeted therapies aimed at improving outcomes for young patients.

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