Pitt Pediatrics congratulates Lisa Maurer, MD, PhD for her recent publication “A small-molecule inhibitor of BCL10-MALT1 interaction abrogates progression of diffuse large B cell lymphoma” published in the Journal of Clinical Investigation. Maurer is an assistant professor of pediatrics and a pediatric oncologist with an interest in pediatric leukemia and lymphoma.
Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and the activated B cell–like subtype (ABC-DLBCL) is associated with particularly poor outcome. MALT1 is the effector protein of the CBM signalosome such that its recruitment to the signalosome via interaction with BCL10 allows it to exert both protease and scaffolding activities that together synergize in driving NF-κB.
In this study, Maurer and the team demonstrate that a molecular groove located between two adjacent immunoglobulin-like domains within MALT1 represents a binding pocket for BCL10. Using this, they performed an in silico screen to identify small molecules that dock within this MALT1 groove and act as BCL10-MALT1 protein-protein interaction (PPI) inhibitors.
Their findings demonstrate that small-molecule inhibitors of BCL10-MALT1 interaction can function as potent agents to block MALT1 signaling in selected lymphomas, and provide a road map for clinical development of a new class of precision-medicine therapeutics.
For more news from the Deparment of Pediatrics and updates for current events, follow us on X, BlueSky and Instagram.