Targeting PAX5 to restore balance in leukaemia cells

Alejandro Vaquero

Institut de Recerca Contra la Leucèmia Josep Carreras, Badalona, Spain

B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancer in children and a serious threat to adults. While treatments have improved, many patients still relapse, especially those with aggressive forms of the disease. PAX5 is a key player in B-cell development, and its abundance is often reduced in B-ALL patients. Boosting its function has been shown to reverse leukemia in lab models however, no effective treatment targeting Pax5 has been developed until now.

This project explores a novel therapeutic strategy based on a mechanism previously identified by the team, which regulates the stability and activity of the PAX5 protein. Rather than targeting PAX5 directly, the approach focuses on activating a regulatory factor that enhances PAX5 stability and function. The team has shown that this factor cooperates with PAX5 in both normal and leukemic cells, and that higher levels of the regulator correlate with better patient outcomes.

To unlock therapeutic potential from this insight, researchers will analyze patient samples, validate the relevance of this mechanism in B-ALL patients, will study the progression of B-ALL using murine models, and screen for compounds capable of safely and effectively activating this pathway. The ultimate goal is to restore the protective role of PAX5 and prevent or reverse disease progression in B-ALL.

• Eduardo Domínguez, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela, Spain

Innovative targeting of PAX5 in B-cell Acute Lymphoblastic Leukaemia

€989.800,00